Skip to main content

Advertisement

Log in

Silencing of lncRNA DLEU1 inhibits tumorigenesis of ovarian cancer via regulating miR-429/TFAP2A axis

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Long non-coding RNAs (lncRNAs) are known as crucial regulators in the development of OC. In the current study, we aim to explore the function and molecular mechanism of lncRNA DLEU1 in OC. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the expression of DLEU1, miR-429, and TFAP2A in OC cells and tissues. The relationship among DLEU1, miR-429, and TFAP2A was tested by dual-luciferase reporter (DLR) assay. Besides, the proliferative, migratory and invasive abilities of OC cells were analyzed by MTT, wound healing, and transwell assays, respectively. Western blot was performed to determine the protein expression of TFAP2A. The expression of lncRNA DLEU1 and TFAP2A were upregulated, and miR-429 was downregulated in OC tissues. Silencing of DLEU1 inhibited the proliferation, migration, and invasion of OC cells. Bioinformation and DLR assay showed that DLEU1 acted as the sponge for miR-429. Moreover, miR-429 could directly target TFAP2A and inhibit the proliferation, migration, and invasion of OC cells. Moreover, we observed a negative correlation between miR-429 and DLEU1, and between miR-429 and TFAP2A in OC tissues. The transfection of miR-429 inhibitor or pcDNA-TFAP2A reversed the inhibitory effects of si-DLEU1 on the proliferation, migration, and invasion of OC cells. Silencing of DLEU1 inhibited the proliferation, migration, and invasion of OC cells by regulating miR-429/TFAP2A axis, indicating a potential therapeutic target for OC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

All data in the manuscript is available through the responsible corresponding author.

References

  1. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A, Siegel RL (2018) Ovarian cancer statistics. Siegel RL (2018) Ovarian cancer statistics 68(4):284–296

    Google Scholar 

  2. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics. CA Cancer Journal for Clinicians 66(1):7–30

    Article  Google Scholar 

  3. Tripathi MK, Doxtater K, Keramatnia F, Zacheaus C, Yallapu MM, Jaggi M, Chauhan SC (2018) Role of lncRNAs in ovarian cancer: defining new biomarkers for therapeutic purposes. Drug Discovery Today 23(9):1635–1643

    Article  CAS  Google Scholar 

  4. Liu J, Matulonis UA (2014) New strategies in ovarian cancer: translating the molecular complexity of ovarian cancer into treatment advances. Clinical Cancer Research 20(20):5150–5156

    Article  CAS  Google Scholar 

  5. Dong P, Xiong Y, Yue J, Hanley SJ, Watari H (2018) miR-34a, miR-424 and miR-513 inhibit MMSET expression to repress endometrial cancer cell invasion and sphere formation. Oncotarget 9(33):23253

    Article  Google Scholar 

  6. Dong P, Xiong Y, Yue J, Hanley SJ, Kobayashi N, Todo Y, Watari H (2018) Long non-coding RNA NEAT1: a novel target for diagnosis and therapy in human tumors. Frontiers Genetics 9:471

    Article  CAS  Google Scholar 

  7. Fritah S, Niclou SP, Azuaje F (2014) Databases for lncRNAs: a comparative evaluation of emerging tools. RNA 20(11):1655–1665

    Article  CAS  Google Scholar 

  8. Gao Y, Meng H, Liu S, Hu J, Zhang Y, Jiao T, Liu Y, Ou J, Wang D, Yao L (2015) LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b. Human Molecular Genetics 24(3):841–852

    Article  CAS  Google Scholar 

  9. Chai Y, Liu J, Zhang Z, Liu L (2016) HuR-regulated lnc RNA NEAT 1 stability in tumorigenesis and progression of ovarian cancer. Cancer Medicine 5(7):1588–1598

    Article  CAS  Google Scholar 

  10. Liu H, Liu G, Pang W, Zhang H, Zeng Z, Wang H (2020) LncRNA LUCAT1 promotes proliferation of ovarian cancer cells by regulating miR-199a-5p expression. Eur Rev Med Pharmacol Sci 24(4):1682–1687

    PubMed  Google Scholar 

  11. Hu Y, Mei X, Tang D (2020) Long non-coding RNA XIST is down-regulated and correlated to better prognosis in ovarian cancer. Math Biosci Eng 17(3):2070

    Article  Google Scholar 

  12. Wang L, Sun K, Wu D, Xiu Y, Chen X, Chen S, Zong Z, Sang X, Liu Y, Zhao Y (2017) DLEU1 contributes to ovarian carcinoma tumourigenesis and development by interacting with miR-490-3p and altering CDK1 expression. J Cell Mol Med 21(11):3055–3065

    Article  CAS  Google Scholar 

  13. Liu S-M, Lin C-H, Lu J, Lin I-Y, Tsai M-S, Chen M-H, Ma N (2018) miR-596 modulates melanoma growth by regulating cell survival and death. J Invest Dermatol 138(4):911–921

    Article  CAS  Google Scholar 

  14. Zhao HM, Wei W, Sun YH, Gao JH, Wang Q, Zheng JH (2015) MicroRNA-9 promotes tumorigenesis and mediates sensitivity to cisplatin in primary epithelial ovarian cancer cells. Tumour Biol 36(9):6867–6873. https://doi.org/10.1007/s13277-015-3399-x

    Article  CAS  PubMed  Google Scholar 

  15. Makino Y, Kawanishi E (1991) High-performance liquid chromatographic separation of human apotransferrin and monoferric and diferric transferrins. J Chromatogr 567(1):248–253. https://doi.org/10.1016/0378-4347(91)80328-a

    Article  CAS  PubMed  Google Scholar 

  16. Zou J, Liu L, Wang Q, Yin F, Yang Z, Zhang W, Li L (2017) Downregulation of miR-429 contributes to the development of drug resistance in epithelial ovarian cancer by targeting ZEB1. Am J Transl Res 9(3):1357–1368

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Chen H, Xia B, Liu T, Lin M, Lou G (2016) KIAA0101, a target gene of miR-429, enhances migration and chemoresistance of epithelial ovarian cancer cells. Cancer Cell Int 16:74. https://doi.org/10.1186/s12935-016-0353-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Meng X, Joosse SA, Müller V, Trillsch F, Milde-Langosch K, Mahner S, Geffken M, Pantel K, Schwarzenbach H (2015) Diagnostic and prognostic potential of serum miR-7, miR-16, miR-25, miR-93, miR-182, miR-376a and miR-429 in ovarian cancer patients. Br J Cancer 113(9):1358–1366

    Article  CAS  Google Scholar 

  19. Zhao H, Yu H, Zheng J, Ning N, Tang F, Yang Y, Wang Y (2018) Lowly-expressed lncRNA GAS5 facilitates progression of ovarian cancer through targeting miR-196-5p and thereby regulating HOXA5. Gynecol Oncol 151(2):345–355. https://doi.org/10.1016/j.ygyno.2018.08.032

    Article  CAS  PubMed  Google Scholar 

  20. Tao P, Yang B, Zhang H, Sun L, Wang Y, Zheng W (2020) The overexpression of lncRNA MEG3 inhibits cell viability and invasion and promotes apoptosis in ovarian cancer by sponging miR-205-5p. Int J Clin Exp Pathol 13(5):869–879

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Yu J, Han Q, Cui Y (2017) Decreased long non-coding RNA SPRY4-IT1 contributes to ovarian cancer cell metastasis partly via affecting epithelial-mesenchymal transition. Tumour Biol. https://doi.org/10.1177/1010428317709129

    Article  PubMed  Google Scholar 

  22. Du W, Feng Z, Sun Q (2018) LncRNA LINC00319 accelerates ovarian cancer progression through miR-423-5p/NACC1 pathway. Biochem Biophys Res Commun 507(1–4):198–202. https://doi.org/10.1016/j.bbrc.2018.11.006

    Article  CAS  PubMed  Google Scholar 

  23. Wang X, Yang B, She Y, Ye Y (2018) The lncRNA TP73-AS1 promotes ovarian cancer cell proliferation and metastasis via modulation of MMP2 and MMP9. J Cell Biochem 119(9):7790–7799. https://doi.org/10.1002/jcb.27158

    Article  CAS  PubMed  Google Scholar 

  24. Lai XJ, Cheng HF (2018) LncRNA colon cancer-associated transcript 1 (CCAT1) promotes proliferation and metastasis of ovarian cancer via miR-1290. Eur Rev Med Pharmacol Sci 22(2):322–328. https://doi.org/10.26355/eurrev_201801_14175

    Article  PubMed  Google Scholar 

  25. Li X, Li Z, Liu Z, Xiao J, Yu S, Song Y (2018) Long non-coding RNA DLEU1 predicts poor prognosis of gastric cancer and contributes to cell proliferation by epigenetically suppressing KLF2. Cancer Gene Ther 25(3–4):58–67. https://doi.org/10.1038/s41417-017-0007-9

    Article  CAS  PubMed  Google Scholar 

  26. Pang B, Sui S, Wang Q, Wu J, Yin Y, Xu S (2019) Upregulation of DLEU1 expression by epigenetic modification promotes tumorigenesis in human cancer. J Cell Physiol 234(10):17420–17432. https://doi.org/10.1002/jcp.28364

    Article  CAS  PubMed  Google Scholar 

  27. Liu C, Tian X, Zhang J, Jiang L (2018) Long non-coding RNA DLEU1 promotes proliferation and invasion by interacting With miR-381 and enhancing HOXA13 expression in cervical cancer. Front Genet 9:629. https://doi.org/10.3389/fgene.2018.00629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A, Bozzoni I (2011) A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell 147(2):358–369. https://doi.org/10.1016/j.cell.2011.09.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu H, Chen R, Kang F, Lai H, Wang Y (2020) KCNQ1OT1 promotes ovarian cancer progression via modulating MIR-142-5p/CAPN10 axis. Mol Genet Genomic Med 8(2):e1077. https://doi.org/10.1002/mgg3.1077

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Li J, Zhang S, Wu L, Pei M (2019) Interaction between LncRNA-ROR and miR-145 contributes to epithelial-mesenchymal transition of ovarian cancer cells. Gen Physiol Biophys 38(6):461–471. https://doi.org/10.4149/gpb_2019028

    Article  CAS  PubMed  Google Scholar 

  31. Dimitrova Y, Gruber AJ, Mittal N, Ghosh S, Dimitriades B, Mathow D, Grandy WA, Christofori G, Zavolan M (2017) TFAP2A is a component of the ZEB1/2 network that regulates TGFB1-induced epithelial to mesenchymal transition. Biol Direct 12(1):8. https://doi.org/10.1186/s13062-017-0180-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Anttila MA, Kellokoski JK, Moisio KI, Mitchell PJ, Saarikoski S, Syrjanen K, Kosma VM (2000) Expression of transcription factor AP-2alpha predicts survival in epithelial ovarian cancer. Br J Cancer 82(12):1974–1983. https://doi.org/10.1054/bjoc.2000.1146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sliwa A, Kubiczak M, Szczerba A, Walkowiak G, Nowak-Markwitz E, Burczynska B, Butler S, Iles R, Bialas P, Jankowska A (2019) Regulation of human chorionic gonadotropin beta subunit expression in ovarian cancer. BMC Cancer 19(1):746. https://doi.org/10.1186/s12885-019-5960-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Xu J, Zheng J, Wang J, Shao J (2019) miR-876-5p suppresses breast cancer progression through targeting TFAP2A. Exp Ther Med 18(2):1458–1464. https://doi.org/10.3892/etm.2019.7689

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Zhou J, Duan H, Xie Y, Ning Y, Zhang X, Hui N, Wang C, Zhang J (2016) MiR-193a-5p targets the coding region of AP-2alpha mRNA and induces cisplatin resistance in bladder cancers. J Cancer 7(12):1740–1746. https://doi.org/10.7150/jca.15620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pu M, Li C, Qi X, Chen J, Wang Y, Gao L, Miao L, Ren J (2017) MiR-1254 suppresses HO-1 expression through seed region-dependent silencing and non-seed interaction with TFAP2A transcript to attenuate NSCLC growth. PLoS Genet 13(7):e1006896. https://doi.org/10.1371/journal.pgen.1006896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Sumigama S, Ito T, Kajiyama H, Shibata K, Tamakoshi K, Kikkawa F, Williams T, Tainsky MA, Nomura S, Mizutani S (2004) Suppression of invasion and peritoneal carcinomatosis of ovarian cancer cells by overexpression of AP-2alpha. Oncogene 23(32):5496–5504. https://doi.org/10.1038/sj.onc.1207723

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

HYX and LYW designed and analyzed the experiment, and was a major contributor in writing the manuscript. HYX, LYW and XLJ performed the experiment. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiuli Jiang.

Ethics declarations

Conflict of interest

The Authors declare that they have no conflicts of interest to disclose.

Ethical approval

This study was approved by the ethics committee of The First People’s Hospital of Lanzhou City (202008-19). Written informed consent was obtained from all subjects.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xu, H., Wang, L. & Jiang, X. Silencing of lncRNA DLEU1 inhibits tumorigenesis of ovarian cancer via regulating miR-429/TFAP2A axis. Mol Cell Biochem 476, 1051–1061 (2021). https://doi.org/10.1007/s11010-020-03971-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-020-03971-9

Keywords

Navigation