Skip to main content
Download PDF
/v1/supplement/title

Analysis of lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 in endometrial cancer

BMC Cancer volume 22, Article number: 343 (2022) Cite this article

Abstract

Background

The analysis of long non-coding RNA (lncRNA) in endometrial cancer is a novel field of science. Although numerous lncRNA sequences have been identified until today, their correlation with endometrial cancer is still undetermined. The aim of this study was to analyze the expression of four lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 and to investigate their significance in endometrial cancer.

Methods

LncRNA sequences were investigated in paraffin blocks (tumor tissue and non-malignant endometrial tissue in archival postoperative specimens) in endometrial cancer patients (Cases, n = 120) and in cancer-free controls (n = 80) using real-time PCR assay.

Results

This study revealed a lower expression of LINC01468 in endometrial cancer patients than in controls. Both LINC01468 and FAM3D-AS1 were positively correlated with Body Mass Index (BMI) in cancer-free controls.

Conclusions

LncRNA LINC01468 may be a protective factor in development of endometrial cancer.

Peer Review reports

Background

Endometrial cancer (EC) is the second most common malignancy of female genitals worldwide after cervical cancer. According to IARC (International Agency for Research on Cancer), in 2020 only more than 400,000 cases and almost 100,000 deaths were reported [1]. As this malignancy poses a serious threat to global health, it has gained global research attention: almost 14,000 original articles on this matter were published from 1900 to 2020 and this number increases continuously [2]. During the greater share of that period scholars’ understanding of EC was strictly constrained and dictated by histopathological representation of the disease: type I endometrioid tumors were associated with estrogen excess, obesity and hormone-receptor positivity, whereas type II non-endometrioid ones (predominantly serous) were less common, lacked hormone-dependency and were labelled with rather a poor prognosis. This classical perception of EC was then challenged in 2013 by a notable paper published in Nature when a completely new light shed on the disease shifted the recognition of EC from histology to genetics with even a thorough reclassification proposed [3].

With the introduction of genetic approach to cancer – as the shift towards genetics is not limited to EC only – some novel research pathways came into exploration, including the analysis of various aspects of human genome and their potential role in carcinogenesis. It is now clear that only less than 2% of DNA is represented by mRNA and bears a protein-coding potential which suggests that genes ‘operate’ in a so called ‘plethora of junk DNA’ [4]. The vast majority of human genome is transcribed into a ‘dark matter’ which was initially believed to be only a ‘transcriptional noise’. However, these inter-genic regions proved to have a considerable significance and have rightly drawn major scientific enthusiasm in recent years [5, 6]. The beforementioned ‘dark matter’ includes, among many others, long non-coding RNA (lncRNA) which is defined as transcripts greater than 200 nucleotides with no evident ability of being translated into protein. Although the role of lncRNA has not been fully elucidated yet, it is well known that it plays a vital part in numerous biological phenomena like epigenetic regulation, genetic imprinting, cell apoptosis and differentiation and even cell cycle control system [7,8,9,10,11,12,13]. Moreover, it regulates RNA maturation, intercellular transport and formation of ribonucleoprotein complexes [6].

It has been also demonstrated, that lncRNA may promote the growth of endometrial tissue outside the uterine cavity and thus it may contribute to development of endometriosis [14]. According to the growing body of literature, primary differences in lncRNA expression have also been found in various types of cancer [6, 15,16,17,18]. Likewise, in EC it has been concluded that some of these non-coding transcripts may be implemented as both diagnostic and prognostic biomarkers of this malignancy [4, 19, 20].

The first in-depth paper on various subtypes of lncRNA in EC was published by Zhai et al. in 2015 [21]. In this study authors have identified 53 distinct lncRNA sequences which expressions statistically significantly differed in carcinomatous endometrium and cancer-free one. Variations in expression concerned also signaling pathways, cell components and numerous other molecular features.

Recent literature data suggest that the following lncRNA sequences are associated with endometrial cancer: ASLNC04080 (SNHG12 – small nucleolar RNA host gene 12) [21], H19 (human H19 gene) [22,23,24], OVAAL (ovarian adenocarcinoma amplified lncRNA) [25], CASC2 (cancer susceptibility candidate 2) [26], MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) [27], HOTAIR (HOX transcript antisense RNA) [28], SRA (steroid receptor RNA activator) [29], Linc-RoR (long intergenic non-coding ribonucleic acids-regulator of programming) [30], LIN00261 [31], LIN00672 [32], 7-lncRNA [33], and many others. It has also been proven, that long non-coding transcripts play some role in proliferation and migration of endometrial cancer cells [34]. Some authors even suggest employing a special algorithm that clusters specific triplets of mRNA, lncRNA and miRNA to better identify the risk of this cancer which may also reflect in deeper understanding of transcriptome regulatory mechanisms in this disease [35].

Although, as presented above, numerous lncRNA sequences are somehow correlated with EC, the exact meaning and context of this interaction remains unclear and calls for elucidation. This paper is designed to expand the still vague and incomplete knowledge of the role of selected lncRNA sequences in EC.

Following lncRNA sequences have been selected for the study: FAM3D-AS1, LINC01230, LINC01315 and LINC01468. There is limited literature data on these lncRNAs, and until now none of them has been studied in endometrial cancer. Current evidence on lncRNA sequences FAM3D-AS1 (FAM3D Antisense RNA 1) and LINC01315 is scarce, but they have been affiliated with certain types of cancer (colon, larynx, pharynx, thyroid, breast, oral squamous and nasopharyngeal) [36,37,38,39,40,41]. LncRNA LINC01468 (also known as LNCAROD - lncRNA activating regulator of DKK1), on the other hand, has been linked to head and neck cancer [42], liver cancer [43] and bladder cancer [44]. The knowledge on lncRNA LINC01230 is rather narrow: it has been reported that is a novel modifier of endothelial function regulated by regulated by PPARγ [45], but no reports on its role in carcinogenesis are to be found.

Methods

Aim of the study

The aim of this study was to analyze the level of expression of four long non-coding RNA sequences (FAM3D-AS1, LINC01230, LINC01315 and LINC01468) in endometrial cancer and to correlate the findings with both clinical and pathological data and with the risk of endometrial cancer.

Patients

Biological material was retrieved from archival post-operative specimens. Endometrial cancer tissue samples (i.e. tumor tissue embedded in paraffin blocks) were obtained from 120 women (Cases) treated surgically for endometrioid EC in the Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, Polish Mother’s Memorial Hospital - Research Institute, Lodz, Poland in the period between 2003 and 2012. Patients were staged according to FIGO [46] and tumor grading (G1, G2, G3) was also assessed. Similarly, endometrial tissue samples (i.e. endometrial tissue embedded in paraffin blocks) from 80 cancer-free women treated surgically for symptomatic uterine fibroids in the abovementioned Institution were selected as Controls. Histopathological analysis of all specimens was performed in Department of Clinical Pathology, Polish Mother’s Memorial Hospital - Research Institute, Lodz, Poland. Genetic assays of FAM3D-AS1, LINC01230, LINC01315 and LINC01468 were performed in Research Laboratory CoreLab, Medical University of Lodz, Lodz, Poland.

Total RNA isolation

Total RNA was extracted from FFPE (Formalin-Fixed Paraffin-Embedded) tissue samples using High Pure miRNA Isolation Kit (Roche Diagnostics GmbH, Mannheim, Germany), as previously described by Wilczyński et al. [47]. In brief, FFPE microsamples were processed in 2 ml Eppendorf tubes, deparaffinized with 100% xylene, washed in 100% ethanol and dried at 55 °C for 10 min. Then, the dried tissue was resuspended in 100 μl Paraffin Tissue Lysis Buffer (included in the kit) and digested overnight with proteinase K at 55 °C. Subsequent steps of RNA purification were performed according to the 1-Column protocol for total RNA purification. Subsequently, 325 μl of Binding Buffer and 325 μl of Binding Enhancer was added and the mixture applied onto the columns, centrifuged for 30 s at 13000 x g and washed twice with 500 μl and 300 μl of Wash Buffer. An additional step of centrifugation for 1 min at 13000 x g was carried out in order to dry filter fleece completely and RNA was eluted with 50 μl of Elution Buffer. The yield and quality (260/280 optical density ratios) of the RNA products were determined using PicoDrop spectrophotometer (Picodrop Limited, Hinxton, UK). The purified total RNA was immediately used for cDNA synthesis or stored at − 80 °C until use.

Reverse transcription

Reverse transcription was carried out using the Maxima First Strand cDNA Synthesis Kit (Thermo Fisher Scientific, Inc., Waltham, MA, USA) according to the manufacturer’s protocols. 500 ng of total RNA was used as starting material, reverse transcription was performed in conditions optimized for use with this kit (25 °C for 10 min, 50 °C for 30 min, 85 °C for 5 min). The cDNA samples were kept frozen at − 20 °C.

Quantification of lncRNA

LncRNA quantification was done using TaqMan™ Non-coding RNA Assay FAM3D-AS1 (lnc-KCTD6–3, Assay ID: Hs04938334_g1), TaqMan™ Gene Expression Assay LINC01230 (linc-DMRT2; lnc-DRMT2; TCONS_00015639, Assay ID Hs05032977_s1), LINC01315 (lnc-C22orf32–1, Assay ID: Hs01674425_m1), LINC01468 (lnc-MBL2–4, Assay ID: Hs01380812_m1. In addition, Gapdh Assay (ID: Hs99999905_m1) was used as an endogenous control. qPCR reactions were performed in 10 μl reaction volumes included 10 ng cDNA, 5 μl TaqMan Fast Advanced PCR Master Mix and 0,5 μl appropriate assay (20x). The reactions were incubated in a 96-well plate at 95 °C for 3 min, followed by 40 cycles of 95 °C for 1 s and 60 °C for 20 s. All reactions were performed in duplicate using a 7900HT Fast Real-Time PCR System (Applied Biosystems; Thermo Fisher Scientific, Inc., Waltham, MA, USA). Relative expression level was determined using to the 2-ΔΔCq method.

Statistical analysis

In order to process the results of lncRNA sequences’ expression, Applied Biosystems DataAssist Software V3.01 Thermo Fisher Scientific – US (https://www.thermofisher.com/pl/en/home/technical-resources/software-downloads/dataassist-software.html) was employed. The significance of differences was analyzed at the level of gene expression and mRNA, using non-parametric tests (the U Mann-Whitney test and the Kruskal-Wallis test) for a lack of distribution normality of the obtained results, as confirmed by the Shapiro-Wilk test. The R-Spearman test was used to assess the correlations between variables. A statistical significance was confirmed at p < 0,05. Statistica 13.3. software was used for statistical analysis of obtained data.

Results

Clinical and pathological data of Cases and Controls are presented in Table 1. The expression of lncRNA FAM3D-AS1, LINC01230, LINC01315 and LINC01468 in Cases and Controls, measured by Relative Quantification (RQ), are presented in Tables (2 and 3) and Figs. (1 and 2), respectively. Our study revealed no statistically significant differences in expression of lncRNA sequences: FAM3D-AS1, LINC01230 and LINC01315 between EC patients and Controls. However, we have revealed a statistically significant lower expression of LINC0148 in Cases (RQ: 6,56) in comparison to Controls (RQ: 69,46) - see Fig. 3. Table 4 presents the comparisons of expressions of the studied lncRNA in Cases and Controls.

Table 1 Clinical and pathological data of Cases and Controls
Full size table
Table 2 Expression of lncRNA sequences in Cases
Full size table
Table 3 Expression of lncRNA sequences in Controls
Full size table
Fig. 1
figure 1

Expression of lncRNA sequences in Cases. Bars represent the mean values of Relative Quantification of studied lncRNA sequences’ expression in endometrial cancer tissue

Full size image
Fig. 2
figure 2

Expression of lncRNA sequences in Controls. Bars represent the mean values of Relative Quantification of studied lncRNA sequences’ expression in non-malignant endometrium

Full size image
Fig. 3
figure 3

Expression of LINC0148 in Cases and Controls, Relative Quantification (RQ). Bars represent the mean values of Relative Quantification of the expression of LINC0148 in endometrial cancer and in non-malignant endometrial tissue. A statistically significant lower expression of LINC0148 was revealed in endometrial cancer patients (Cases)

Full size image
Table 4 Correlation of expressions of lncRNA of the studied lncRNA sequences in Cases and Controls, Mann–Whitney U test, p < 0,05
Full size table

Expression of lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 has been also analyzed in terms of correlation with clinical and pathological data of Cases: age, Body Mass Index (BMI), parity, use of hormone replacement therapy (HRT), cancer Grading and Staging - no statistically significant correlation was observed here. Interestingly, the study revealed a statistically significant correlation between the Body Mass Index (BMI) and two lncRNA sequences within Controls: both FAM3D-AS1 and LINC0148 are positively correlated with Controls’ BMI: R – Spearman: 0,252 and 0,260, respectively (see Table 5). Table 5 and Figs. (4 and 5) present the correlation of FAM3D-AS1 and LINC0148 with BMI. The other two studied sequences – LINC01230 and LINC01315 – presented no meaningful correlation with BMI in Controls. Alike, no correlation was observed between clinical and pathological data (age, BMI, parity, use of hormone replacement therapy) and studied lncRNA sequences in Controls.

Table 5 Correlation between studied lncRNA sequences and Body Mass Index (BMI) in Controls, Spearman’s rank correlation coefficient, p < 0,05
Full size table
Fig. 4
figure 4

Correlation between FAM3D-AS1 and Body Mass Index (BMI) in Controls. The graph represents the distribution of Relative Quantification of FAM3D-AS1 in cancer-free patients. In our study FAM3D-AS1 was positively correlated with Controls’ BMI

Full size image
Fig. 5
figure 5

Correlation between LINC01468 and Body Mass Index (BMI) in Controls. The graph represents the distribution of Relative Quantification of LINC01468 in cancer-free patients. In our study LINC01468 was positively correlated with Controls’ BMI

Full size image

Discussion

In the Introduction we have presented a wide assortment of current literature data to deliver compelling evidence that transcription of lncRNA plays a considerable role in key biological processes in cancer. Some sequences of this non-coding transcripts have been already studied in endometrial cancer, but this area of research still stands mostly unexplored.

In our study we have presented an analysis of expression of FAM3D-AS1, LINC01230, LINC01315 and LINC01468 in EC patients compared to non-cancerous Controls with an eventual aim to correlate these lncRNA with the risk of this malignancy as well as with clinical and pathological data of studied Cases and Controls. According to the available body of literature, these sequences have not been yet investigated in endometrial cancer. Hence, our research is an original and unprecedented attempt to provide new data on the significance of these transcripts in EC.

Three out of four studied by us sequences (FAM3D-AS1, LINC01230, LINC01315) were found to be statistically irrelevant in terms of endometrial cancer risk and all clinical and pathological data presented in Table 1. It is worthwhile to mention, that the literature data on FAM3D-AS1 and cancer is scarce, and all that is known now is that it may inhibit the development of colorectal cancer and that it is related to the cancer of pharynx and larynx [36, 37]. Yet, potential issues have been raised over the scientific validity of the former finding [48]. In a wider context, one must bear in mind, that colorectal and endometrial cancers - in some cases - share a common background: Lynch Syndrome [49]. The available data on other two sequences (LINC01230 and LINC01315) is not abundant either. Although as little as 5 original papers on the latter are to be found in PubMed database and they cover a spectrum of some cancers there is no research data whatsoever on the role of the former sequence in cancer.

The only lncRNA sequence where our statistical analysis revealed a meaningful correlation with endometrial cancer was LINC01468. In Cases this sequence showed a clear downregulation which may suggest that it acts as a protective factor against this malignancy. Yet, LINC01468 lacked statistical significance in terms of interrelationship with clinical and pathological data of Cases. Although this sequence has not been studied in endometrial cancer, there are other long non-coding transcripts that are not only related to EC itself, but to patients’ clinical and pathological features, i.e. Staging [50]. It only encourages to draw a conclusion that the investigation of selected lncRNA sequences is supported by convincing rationale and research in this field should continue.

Upon extended statistical analysis of our data, we have revealed a positive correlation between two lncRNA sequences (FAM3D-AS1 and LINC01468) and Body Mass Index in Controls. This is an interesting finding if one considers that our non-cancerous control group consisted of patients operated on in our Institution for symptomatic uterine fibroids. Despite the lack of proper literature data on the abovementioned non-coding sequences in uterine fibroids alone, there is some evidence that confirms the positive correlation between obesity and uterine fibroids [51, 52]. But how in detail and why FAM3D-AS1 and LINC01468 are in our study statistically correlated within BMI-adjusted subgroups of our Controls – remains unclear.

However, there are some limitations of our study that need to be mentioned and considered with criticism. The dominant shortcoming of our analysis are numbers: a genetic research study on 120 Cases and 80 Controls (800 assays in total) makes an experienced researcher draw final conclusions with care and skepticism. Especially in genetics, our groups may be simply quantitatively unsatisfactory to conduct a fair judgement. Secondly, the Cases and Controls are not exactly homogenous – to some extent they differ by age, parity, BMI and use of hormone replacement therapy which may bias the results. Moreover, Cases do not constitute a group of disease-free women, but they were all treated surgically due to a benign gynecological condition – symptomatic uterine fibroids. Some reports suggest that some lncRNA sequences (i.e. lncRNA SRA1 and H19) may exhibit a correlation with uterine fibroids’ tissue as such [53, 54], yet in our study the genetic assays were performed strictly on the selected endometrial tissue samples and not on fibroids nor myometrial tissue themselves.

Thirdly, still very little is known on the role of this non-coding ‘transcriptional noise’ and how to thoughtfully design a study to draw final and defensible conclusions. To bring limitations to a close, one needs to point out, that this analysis involved only endometrioid endometrial cancer with type II (non-endometrioid cancer) listed as the main exclusion criterion. Though, it is the latter that remains a real clinical challenge for healthcare providers in gynecological oncology.

Having in mind all the abovementioned findings and aware of the restrictions of our study, we dare to claim that this research has shed some new light on lncRNA in endometrial cancer and contributes to the growing – but still fragmentary – body of knowledge on these non-coding sequences in gynecological oncology.

Conclusions

LINC01468 may be a protective factor in endometrial cancer. The current state of knowledge on lncRNA in cancer, especially in endometrial cancer, is still limited. Further studies are warranted to further explore this subject.

Availability of data and materials

All data generated or analyzed during this study are included in its supplementary information files.

Abbreviations

lncRNA:

Long non-coding RNA

BMI:

Body Mass Index

EC:

Endometrial cancer

IARC:

International Agency for Research on Cancer

SNHG12 :

Small nucleolar RNA host gene 12

H19 :

Human H19 gene

OVAAL :

Ovarian adenocarcinoma amplified lncRNA

CASC2 :

Cancer susceptibility candidate 2

MALAT1 :

Metastasis-associated lung adenocarcinoma transcript 1

HOTAIR :

HOX transcript antisense RNA

SRA :

Steroid receptor RNA activator

Linc-RoR :

Long intergenic non-coding ribonucleic acids-regulator of programming

FFPE tissue sample:

Formalin-Fixed Paraffin-Embedded tissue sample

References

  1. . https://gco.iarc.fr/today/data/factsheets/cancers/24-Corpus-uteri-fact-sheet.pdf. Accessed 24 July 2021.

  2. Brüggmann D, Ouassou K, Klingelhöfer D, Bohlmann MK, Jaque J, Groneberg DA. Endometrial cancer: mapping the global landscape of research. J Transl Med. 2020;18(1):386. https://doi.org/10.1186/s12967-020-02554-y PMID: 33046107; PMCID: PMC7552455.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cancer Genome Atlas Research Network, Kandoth C, Schultz N, Cherniack AD, Akbani R, Liu Y, et al. Integrated genomic characterization of endometrial carcinoma. Nature. 2013;497(7447):67–73. https://doi.org/10.1038/nature12113 Erratum in: Nature. 2013 Aug 8;500(7461):242. PMID: 23636398; PMCID: PMC3704730.

    Article  CAS  Google Scholar 

  4. Hajjari M, Khoshnevisan A, Shin YK. Molecular function and regulation of long non-coding RNAs: paradigms with potential roles in cancer. Tumour Biol. 2014;35(11):10645–63. https://doi.org/10.1007/s13277-014-2636-z Epub 2014 Sep 30. PMID: 25266799.

    Article  CAS  PubMed  Google Scholar 

  5. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, et al. RNA maps reveal new RNA classes and a possible function for pervasive transcription. Science. 2007;316(5830):1484–8. https://doi.org/10.1126/science.1138341 Epub 2007 May 17. PMID: 17510325.

    Article  CAS  PubMed  Google Scholar 

  6. Mitra SA, Mitra AP, Triche TJ. A central role for long non-coding RNA in cancer. Front Genet. 2012;3:17. https://doi.org/10.3389/fgene.2012.00017 Published 2012 Feb 15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yang Y, Ren M, Song C, Li D, Soomro SH, Xiong Y, et al. LINC00461, a long non-coding RNA, is important for the proliferation and migration of glioma cells. Oncotarget. 2017;8(48):84123–39. https://doi.org/10.18632/oncotarget.20340 PMID: 29137410; PMCID: PMC5663582.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Tian D, Sun S, Lee JT. The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell. 2010;143(3):390–403. https://doi.org/10.1016/j.cell.2010.09.049 PMID: 21029862; PMCID: PMC2994261.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sleutels F, Zwart R, Barlow DP. The non-coding air RNA is required for silencing autosomal imprinted genes. Nature. 2002;415(6873):810–3. https://doi.org/10.1038/415810a PMID: 11845212.

    Article  CAS  PubMed  Google Scholar 

  10. Mattick JS, Amaral PP, Dinger ME, Mercer TR, Mehler MF. RNA regulation of epigenetic processes. Bioessays. 2009;31(1):51–9. https://doi.org/10.1002/bies.080099 PMID: 19154003.

    Article  CAS  PubMed  Google Scholar 

  11. Wapinski O, Chang HY. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21(6):354–61. https://doi.org/10.1016/j.tcb.2011.04.001 Epub 2011 May 6. Erratum in: Trends Cell Biol. 2011 Oct;21(10):561. PMID: 21550244.

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, He L, Du Y, Zhu P, Huang G, Luo J, et al. The long noncoding RNA lncTCF7 promotes self-renewal of human liver cancer stem cells through activation of Wnt signaling. Cell Stem Cell. 2015;16(4):413–25. https://doi.org/10.1016/j.stem.2015.03.003 PMID: 25842979.

    Article  CAS  PubMed  Google Scholar 

  13. Ramos AD, Andersen RE, Liu SJ, et al. The long noncoding RNA Pnky regulates neuronal differentiation of embryonic and postnatal neural stem cells. Cell Stem Cell. 2015;16(4):439–47. https://doi.org/10.1016/j.stem.2015.02.007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu Y, Huang X, Lu D, Feng Y, Xu R, Li X, et al. LncRNA SNHG4 promotes the increased growth of endometrial tissue outside the uterine cavity via regulating c-Met mediated by miR-148a-3p. Mol Cell Endocrinol. 2020;514:110887. https://doi.org/10.1016/j.mce.2020.110887 Epub 2020 Jun 7. PMID: 32525017.

    Article  CAS  PubMed  Google Scholar 

  15. Xu S, Kong D, Chen Q, Ping Y, Pang D. Oncogenic long noncoding RNA landscape in breast cancer. Mol Cancer. 2017;16(1):129. https://doi.org/10.1186/s12943-017-0696-6 PMID: 28738804; PMCID: PMC5525255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Shi J, Dong B, Cao J, Mao Y, Guan W, Peng Y, et al. Long non-coding RNA in glioma: signaling pathways. Oncotarget. 2017;8:27582–92.

    Article  Google Scholar 

  17. Zhu J, Han S. Downregulation of LncRNA DARS-AS1 Inhibits the Tumorigenesis of Cervical Cancer via Inhibition of IGF2BP3. Onco Targets Ther. 2021;14:1331–40. https://doi.org/10.2147/OTT.S274623 PMID: 33658798; PMCID: PMC7920590.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Zhang L, Li G, Wang X, Zhang Y, Huang X, Wu H. lncRNA SNHG3 acts as oncogene in ovarian cancer through miR-139-5p and Notch1. Oncol Lett. 2021;21(2):122. https://doi.org/10.3892/ol.2020.12383 Epub 2020 Dec 17. PMID: 33552243; PMCID: PMC7798025.

    Article  CAS  PubMed  Google Scholar 

  19. Li BL, Wan XP. The role of lncRNAs in the development of endometrial carcinoma. Oncol Lett. 2018;16:3424–9.

    PubMed  PubMed Central  Google Scholar 

  20. Liu H, Wan J, Chu J. Long non-coding RNAs and endometrial cancer. Biomed Pharmacother. 2019;119:109396.

    Article  CAS  Google Scholar 

  21. Zhai W, Li X, Wu S, Zhang Y, Pang H, Chen W. Microarray expression profile of lncRNAs and the upregulated ASLNC04080 lncRNA in human endometrial carcinoma. Int J Oncol. 2015;46:2125–37.

    Article  CAS  Google Scholar 

  22. Lottin S, Adriaenssens E, Berteaux N, Leprêtre A, Vilain MO, Denhez E, et al. The human H19 gene is frequently overexpressed in myometrium and stroma during pathological endometrial proliferative events. Eur J Cancer. 2005;41:168–77.

    Article  CAS  Google Scholar 

  23. Yan L, Zhou J, Gao Y, Ghazal S, Lu L, Bellone S, et al. Regulation of tumor cell migration and invasion by the H19/let-7 axis is antagonized by metformin-induced DNA methylation. Oncogene. 2015;34:3076–84.

    Article  CAS  Google Scholar 

  24. Tanos V, Ariel I, Prus D, De-Groot N, Hochberg A. H19 and IGF2 gene expression in human normal, hyperplastic and malignant endometrium. Int J Gynecol Cancer. 2004;14:521–5.

    Article  CAS  Google Scholar 

  25. Akrami R, Jacobsen A, Hoell J, Schultz N, Sander C, Larsson E. Comprehensive analysis of long non-coding RNAs in ovarian cancer reveals global patterns and targeted DNA amplification. Plos One. 2013;12:e80306.

    Article  Google Scholar 

  26. Baldinu P, Cossu A, Manca A, Satta MP, Sini MC, Palomba G, et al. CASC2a gene is down-regulated in endometrial cancer. Anticancer Res. 2007;27:235–43.

    CAS  PubMed  Google Scholar 

  27. Zhao Y, Yang Y, Trovik J, Sun K, Zhou L, Jiang P, et al. A novel wnt regulatory axis in endometrioid endometrial cancer. Cancer Res. 2014;74:5103–17.

    Article  CAS  Google Scholar 

  28. You QY, Tao H, Ling B. Long noncoding RNA HOX transcript antisense intergenic RNA (HOTAIR) as a foe and novel potential therapeutic target for endometrial carcinoma. Int J Gynecol Cancer. 2014;24:1536.

    Article  Google Scholar 

  29. Lanz RB, Chua SS, Barron N, Söder BM, DeMayo F, O'Malley BW. Steroid receptor RNA activator stimulates proliferation as well as apoptosis in vivo. Mol Cell Biol. 2003;23:7163–76.

    Article  CAS  Google Scholar 

  30. Zhou X, Gao Q, Wang J, Zhang X, Liu K, Duan Z. Linc-RNA-RoR acts as a ‘sponge’ against mediation of the differentiation of endometrial cancer stem cells by microRNA-145. Gynecol Oncol. 2014;133:333–9.

    Article  CAS  Google Scholar 

  31. Fang Q, Sang L, Du S. Long noncoding RNA LINC00261 regulates endometrial carcinoma progression by modulating miRNA/FOXO1 expression. Cell Biochem Funct. 2018;36:323–30.

    Article  CAS  Google Scholar 

  32. Li W, Li H, Zhang L, Hu M, Li F, Deng J, et al. Long non-coding RNA LINC00672 contributes to p53 protein-mediated gene suppression and promotes endometrial cancer chemosensitivity. J Biol Chem. 2017;292:5801–13.

    Article  CAS  Google Scholar 

  33. Ouyang D, Li R, Li Y, Zhu X. A 7-lncRNA signature predict prognosis of uterine corpus endometrial carcinoma. J Cell Biochem. 2019;120(10):18465–77. https://doi.org/10.1002/jcb.29164 Epub 2019 Jun 6. PMID: 31168849.

    Article  CAS  PubMed  Google Scholar 

  34. Huang J, Ke P, Guo L, Wang W, Tan H, Liang Y, et al. Lentivirus-mediated RNA interference targeting the long noncoding RNA HOTAIR inhibits proliferation and invasion of endometrial carcinoma cells in vitro and in vivo. Int J Gynecol Cancer. 2014;24:635–42.

    Article  Google Scholar 

  35. Liu C, Zhang YH, Deng Q, Li Y, Huang T, Zhou S, et al. Cancer-Related Triplets of mRNA-lncRNA-miRNA Revealed by Integrative Network in Uterine Corpus Endometrial Carcinoma. Biomed Res Int. 2017;2017:3859582. https://doi.org/10.1155/2017/3859582 Epub 2017 Feb 8. PMID: 28280730; PMCID: PMC5320387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Meng Y, Yu F. Long noncoding RNA FAM3D-AS1 inhibits development of colorectal cancer through NF-κB signaling pathway. Biosci Rep. 2019;39(7):BSR20190724. https://doi.org/10.1042/BSR20190724 PMID: 31147452; PMCID: PMC6609597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zou AE, Ku J, Honda TK, et al. Transcriptome sequencing uncovers novel long noncoding and small nucleolar RNAs dysregulated in head and neck squamous cell carcinoma. RNA. 2015;21(6):1122–34. https://doi.org/10.1261/rna.049262.114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Chen FB, Wu P, Zhou R, Yang QX, Zhang X, Wang RR, et al. LINC01315 Impairs microRNA-211-Dependent DLG3 Downregulation to Inhibit the Development of Oral Squamous Cell Carcinoma. Front Oncol. 2020;10:556084. https://doi.org/10.3389/fonc.2020.556084 PMID: 33117688; PMCID: PMC7549330.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Liang R, Zhang J, Zhang RM, Qiu H. LINC01315 silencing inhibits the aggressive phenotypes of colorectal carcinoma by sponging miR-205-3p. Biochem Biophys Res Commun. 2021;534:1033–9. https://doi.org/10.1016/j.bbrc.2020.10.041 Epub 2020 Nov 6. PMID: 33162032.

    Article  CAS  PubMed  Google Scholar 

  40. Ren J, Zhang FJ, Wang JH, Tang JD. LINC01315 promotes the aggressive phenotypes of papillary thyroid cancer cells by sponging miR-497-5p. Kaohsiung J Med Sci. 2021;37(6):459–67. https://doi.org/10.1002/kjm2.12369 Epub 2021 Feb 20. PMID: 33611825.

    Article  CAS  PubMed  Google Scholar 

  41. Xue J, Huang S, Chen J, Y-z C, Shao Z-m WJ, Chi Y. Overexpression of long non-coding RNA Linc01315 predicts poor prognosis in breast Cancer. Front Oncol. 2021;11:562378. https://doi.org/10.3389/fonc.2021.562378.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Ban Y, Tan P, Cai J, Li J, Hu M, Zhou Y, et al. LNCAROD is stabilized by m6A methylation and promotes cancer progression via forming a ternary complex with HSPA1A and YBX1 in head and neck squamous cell carcinoma. Mol Oncol. 2020;14(6):1282–96. https://doi.org/10.1002/1878-0261.12676 Epub 2020 Apr 13. PMID: 32216017; PMCID: PMC7266281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Jia G, Wang Y, Lin C, Lai S, Dai H, Wang Z, et al. LNCAROD enhances hepatocellular carcinoma malignancy by activating glycolysis through induction of pyruvate kinase isoform PKM2. J Exp Clin Cancer Res. 2021, 299;40(1). https://doi.org/10.1186/s13046-021-02090-7 PMID: 34551796; PMCID: PMC8459495.

  44. Gao X, Zhang S, Chen Y, Wen X, Chen M, Wang S, et al. Development of a novel six-long noncoding RNA signature predicting survival of patients with bladder urothelial carcinoma. J Cell Biochem. 2019;120(12):19796–809. https://doi.org/10.1002/jcb.29285 Epub 2019 Jul 24. PMID: 31338862.

    Article  CAS  PubMed  Google Scholar 

  45. Liu L, Wang Z, Jia J, Shi Y, Lian T, Han X. Linc01230, transcriptionally regulated by PPARγ, is identified as a novel modifier in endothelial function. Biochem Biophys Res Commun. 2018;507(1–4):369–76. https://doi.org/10.1016/j.bbrc.2018.11.045 Epub 2018 Nov 16. PMID: 30454889.

    Article  CAS  PubMed  Google Scholar 

  46. Lewin SN. Revised FIGO staging system for endometrial cancer. Clin Obstet Gynecol. 2011;54(2):215–8. https://doi.org/10.1097/GRF.0b013e3182185baa PMID: 21508690.

    Article  PubMed  Google Scholar 

  47. Wilczyński M, Żytko E, Szymańska B, et al. Expression of miR-146a in patients with ovarian cancer and its clinical significance. Oncol Lett. 2017;14(3):3207–14. https://doi.org/10.3892/ol.2017.6477.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Expression of Concern: Long non coding RNA FAM3D-AS1 inhibits development of colorectal cancer through NF-kB signaling pathway. Biosci Rep. 2021;41(4). https://doi.org/10.1042/BSR-20190724_EOC.

  49. Ryan NA, RF MM, Ramchander NC, Seif MW, Evans DG, Crosbie EJ. Lynch syndrome for the gynaecologist. Obstet Gynaecol. 2021;23(1):9–20. https://doi.org/10.1111/tog.12706 Epub 2021 Jan 18. PMID: 33679238; PMCID: PMC7898635.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Li X, Pang L, Yang Z, Liu J, Li W, Wang D. LncRNA HOTAIRM1/HOXA1 Axis Promotes Cell Proliferation, Migration And Invasion In Endometrial Cancer. Onco Targets Ther. 2019;12:10997–1015.

    Article  CAS  Google Scholar 

  51. Moore AB, Flake GP, Swartz CD, Heartwell G, Cousins D, Haseman JK, et al. Association of race, age and body mass index with gross pathology of uterine fibroids. J Reprod Med. 2008;53(2):90–6 PMID: 18357799.

    PubMed  Google Scholar 

  52. Sun K, Xie Y, Zhao N, Li Z. A case-control study of the relationship between visceral fat and development of uterine fibroids. Exp Ther Med. 2019;18:404–10.

    PubMed  PubMed Central  Google Scholar 

  53. Akbari M, Yassaee F, Aminbeidokhti M, Abedin-Do A, Mirfakhraie R. LncRNA SRA1 may play a role in the uterine leiomyoma tumor growth regarding the MED12 mutation pattern. Int J Womens Health. 2019;11:495–500. https://doi.org/10.2147/IJWH.S211632 PMID: 31507331; PMCID: PMC6718952.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Cao T, Jiang Y, Wang Z, Zhang N, Al-Hendy A, Mamillapalli R, et al. H19 lncRNA identified as a master regulator of genes that drive uterine leiomyomas. Oncogene. 2019;38(27):5356–66. https://doi.org/10.1038/s41388-019-0808-4 Epub 2019 May 15. PMID: 31089260; PMCID: PMC6755985.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This research was funded by an internal funding grant of Polish Mother’s Memorial Hospital - Research Institute, Lodz, Poland.

Author information

Authors and Affiliations

  1. Department of Operative Gynecology, Endoscopy and Gynecologic Oncology, Polish Mother’s Memorial Hospital - Research Institute, 281/289, Rzgowska Street, 93-338, Lodz, Poland

    Jan Bieńkiewicz & Miłosz Wilczyński

  2. Department of Clinical Pathology, Polish Mother’s Memorial Hospital - Research Institute, Lodz, Poland

    Hanna Romanowicz & Beata Smolarz

  3. Research Laboratory CoreLab, Medical University of Lodz, Lodz, Poland

    Bożena Szymańska

  4. Department of Molecular Bases of Medicine, Medical University of Lodz, Lodz, Poland

    Daria Domańska-Senderowska

  5. Department of Obstetrics, Perinatology and Gynecology, Polish Mother’s Memorial Hospital - Research Institute, Lodz, Poland

    Anna Stepowicz

  6. Department of Operative and Endoscopic Gynecology, Medical University of Lodz, Lodz, Poland

    Andrzej Malinowski

Authors
  1. Jan Bieńkiewicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hanna Romanowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bożena Szymańska
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daria Domańska-Senderowska
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Miłosz Wilczyński
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna Stepowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andrzej Malinowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Beata Smolarz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JB – study conceptualization, data collection, manuscript writing, edition and revision. HR – study concept, scientific supervision. BSz – genetic assays. MW – data collection, manuscript editing. AS – manuscript edition and revision. AM - study conceptualization, scientific supervision. DD-S – statistical analysis, figures. BS – study conceptualization, scientific supervision. The author(s) read and approved the final manuscript.

Corresponding author

Correspondence to Jan Bieńkiewicz.

Ethics declarations

Ethics approval and consent to participate

Local Ethical Committee by Polish Mother’s Memorial Hospital - Research Institute, Lodz, Poland approved the design of the study (Approval no. 87/2019). A written informed consent was obtained from each participant. All experimental methods in the study abide by the Helsinki Declaration.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bieńkiewicz, J., Romanowicz, H., Szymańska, B. et al. Analysis of lncRNA sequences: FAM3D-AS1, LINC01230, LINC01315 and LINC01468 in endometrial cancer. BMC Cancer 22, 343 (2022). https://doi.org/10.1186/s12885-022-09426-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12885-022-09426-2

Keywords