Original articleLong non-coding RNA UCA1 promotes the tumorigenesis in pancreatic cancer
Introduction
Pancreatic cancer (PC), a common digestive tumor, is the sixth leading cause of cancer-related deaths in the world [1]. Despite the surgical techniques for treatment including surgery, chemotherapy and radiotherapy, the 5-year overall survival rate is still less than 5% [2], [3]. It is characterized by a high tendency for aggressive invasion and distant metastasis, resulting in a high mortality rate. Because of the lack of early symptoms and early detection, PC patients are usually diagnosed at an advanced stage [4]. Thus it is an urgent need to identify new potential biomarkers which can identify biological characteristics of tumors, and predict prognosis and response to therapy.
Long non-coding RNAs (lncRNAs) are a class of transcripts longer than 200 nucleotides, which are typically transcribed by RNA polymerase II [5], [6], [7]. Accumulating evidence have showed that lncRNAs participate in the regulation of various biological processes, such as cell proliferation, differentiation and chromosome inactivation [8], [9]. Moreover, several studies have demonstrated that down-regulated of lncRNAs or aberrant lncRNAs expression can be potentially used as biomarkers for PC [10], [11].
Urothelial cancer-associated 1 (UCA1) is an originally identified non-coding RNA, whose expression correlated with the tumorigenesis of bladder cancer [12]. Subsequently, several studies demonstrated that UCA1 could serve as tumor-promoters in bladder cancer, urothelial carcinoma, breast cancer, colorectal cancer and gastric cancer [13], [14], [15], [16]. For example, Huang et al. found that UCA1 could suppress the tumor suppressor p27 through combining hnRNP I and promoting breast cancer cell growth in vitro and vivo [14]. Li et al. confirmed that UCA1 expression was an independent marker for predicting the prognosis of esophageal squamous cell carcinoma [17]. However, the expression of UCA1 in PC, and a link between UCA1 and tumor clinicopathological characteristics have not been reported until now.
In the present study, we detected the expression of UCA1 in PC tissues and cell lines. Clinicopathological and prognostic values of UCA1 in PC patients were also investigated. Furthermore, we also explored whether abnormal expression of UCA1 regulated cell proliferation, apoptosis and cell cycle in PC cells.
Section snippets
Patients and specimens
A total of 128 PC samples and matched adjacent non-tumor tissues were obtained at the Department of General Surgery, Ningbo No. 2 Hospital from 2006 to 2009. Each patient was histopathologically diagnosed as PC. All patients received operation as initial systemic treatment. The inclusion criteria were as follows: 1) patients with PC confirmed by histopathology with radical operation; 2) patients received operation as initial systemic treatment. Patients who had received preoperative neoadjuvant
UCA1expressions in PC specimens and cell lines
In a preliminary experiment, we assessed the levels of UCA1 in 128 PC tissues and their matched adjacent non-tumor tissues. Our data implied that the relative expression of UCA1 in cancer tissues of PC patients (median expression level: 2.74, range 1.91–3.58) was significantly higher than that in matched NATs (median expression level: 1.55, range1.22–1.87) (p < 0.05, Fig. 1a). Besides, we examined the expression of UCA1 in 4 PC cell lines (Panc-1, Bxpc-3, Capan-1, SW-1990) and the normal
Discussion
It is well known that protein-coding genes account for only 2% of the human genome, whereas over 90% of human genome transcriptional products are non-coding RNAs [20], [21]. To date, accumulating studies have reported that lncRNAs have been involved in several cell behaviors, such as embryonic development, differentiation, apoptosis and motility [22], [23], [24]. Meanwhile, Dys-regulations of lncRNAs have been shown to associate with the modulation of proliferation and invasion of tumors [25].
Conflict of interest
The authors declare that they have no conflicts of interest concerning this article.
Acknowledgements
This study was supported by grants from the National youthful Science Foundation of China (No. 81302147) and the Subject Project of the Construction of the Regional Special Disease Center of Zhejiang Province (No. 2014-98).
References (33)
- et al.
Cancer statistics: current diagnosis and treatment of pancreatic cancer in Shanghai, China
Cancer Lett.
(2014) - et al.
UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion
FEBS Lett.
(2008) - et al.
UCA1, a long non-coding RNA up-regulated in colorectal cancer influences cell proliferation, apoptosis and cell cycle distribution
Pathology (Phila.)
(2014) Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta C(T)) Method
Methods
(2001)- et al.
Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells
J. Biol. Chem.
(2015) - et al.
Cancer statistics 2014
CA. Cancer J. Clin.
(2014) - et al.
New advances in the treatment of metastatic pancreatic cancer
Digestion
(2015) - et al.
Pancreatic cancer: advances in treatment
World J. Gastroenterol.
(2014) - et al.
Pseudogene-derived lncRNAs: emerging regulators of gene expression
Front. Genet.
(2014) - et al.
The functional characterization of long noncoding RNA SPRY4-IT1 in human melanoma cells
Oncotarget
(2014)
Long non-coding RNAs function annotation: a global prediction method based on bi-colored networks
Nucleic Acids Res.
A long non-coding RNA promotes full activation of adult gene expression in the chicken alpha-globin domain
Epigenetics
Identification of differentially expressed long noncoding RNAs in bladder cancer
Clin. Cancer Res.
Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer
Tumour Biol.
A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1alpha in pancreatic ductal adenocarcinoma
Br. J. Cancer
Long non-coding RNA UCA1a(CUDR) promotes proliferation and tumorigenesis of bladder cancer
Int. J. Oncol.
Cited by (68)
Long non-coding RNAs and pancreatic cancer: A multifaceted view
2023, Biomedicine and PharmacotherapyBiogenesis, classification, and role of LncRNAs in tumor angiogenesis: A focus on tumor and its neighbouring cells, and interaction with miRNAs
2022, Process BiochemistryCitation Excerpt :Evidence suggests that inhibiting bladder cancer growth by silencing the lncRNA UCA1 using CRISPR/Cas9 is feasible [61]. Notably, lncRNA UCA1 is also abundantly expressed in PC, and its downregulation has been shown to effectively inhibit PC cell growth, increase apoptosis, and cause cell cycle arrest [7]. Based on these hints, we considered the feasibility of using CRISPR/Cas9 to suppress UCA1 expression as a tumor therapy.
Emerging roles of long noncoding RNAs in chemoresistance of pancreatic cancer
2022, Seminars in Cancer BiologyCitation Excerpt :LncRNA urothelial carcinoma-associated 1 (UCA1) is a 1.4 kb long transcript that is located on 19p13.12 positive strand, which was originally recognized in human bladder cancer cell line [137]. LncRNA UCA1 was reported to promote proliferation, inhibit apoptotic rate and cell cycle arrest in pancreatic cancer [138]. LncRNA UCA1 targets miR-107 and subsequently promotes ITGA2 expression and increases migration and invasion of pancreatic cancer cells [139].
A comprehensive review of the role of long non-coding RNAs in organs with an endocrine function
2020, Biomedicine and PharmacotherapyUCA1 long non-coding RNA: An update on its roles in malignant behavior of cancers
2019, Biomedicine and PharmacotherapyNovel Approach to Enriching Glycosylated RNAs: Specific Capture of GlycoRNAs via Solid-Phase Chemistry
2023, Analytical Chemistry