Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.4)
Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 7, July, p. 777–784

doi: 10.17219/acem/121933

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

The effects of miR-140-5p on the biological characteristics of ovarian cancer cells through the Wnt signaling pathway

Yunyu Wu1,A,B,E,F, Jie Li2,B,C,D,E,F, Shuying Chen3,B,C,D, Zhiwu Yu3,A,B,C

1 Department of Gynecology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China

2 Department of Intensive Care Unit, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

3 Department of Clinical Laboratory, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, China


Background. Ovarian cancer is usually not diagnosed until the late stage, and it is resistant to platinum and other standard chemotherapy drugs, resulting in high mortality.
Objectives. To investigate the effects of miR-140-5p on cell proliferation, apoptosis, invasion, and migration capability in the SKOV3 and OVCAR3 ovarian cancer cell lines through Wnt signaling pathway.
Material and Methods. Expression levels of miR-140-5p were checked using quantitative real-time polymerase chain reaction (qRT-PCR). The expression of miR-140-5p was upregulated by transfecting cells with a miR-140-5p mimic or a mimic negative control (NC). Cell proliferation was assessed using a CCK8 assay, and cell cycle distribution and apoptosis percentage were detected with flow cytometry. A transwell invasion assay was employed to evaluate cell migration and invasion ability. The target complementary relationship between miR-140-5p and WNT1 was verified using a dual-luciferase reporter assay while â-catenin in the nuclei was observed using immunofluorescence. The expression of Wnt signaling pathway-related proteins was examined using western blot and qRT-PCR.
Results. The relative expression level of miR-140-5p in SKOV3 and OVCAR3 cells was obviously decreased compared with that in the IOSE80 cells (p < 0.05). Besides, upregulated miR-140-5p effectively suppressed cell proliferation and increased the apoptosis ratio of SKOV3 and OVCAR3 cells (p < 0.05). In addition, the invasion and migration capability of SKOV3 and OVCAR3 cells in miR-140-5p mimic group was largely suppressed compared with the NC group (p < 0.05). What is more, the target complementary relationship between miR-140-5p and the WNT1 gene was revealed; upregulated miR-140-5p suppressed the expression of Wnt signaling-related genes, and restrained nuclear transfer of â-catenin (p < 0.05).
Conclusion. The overexpression of miR-140-5p restricted the proliferation, migration and invasion abilities, and accelerated cell apoptosis in ovarian cancer cell lines SKOV3 and OVCAR3 through the Wnt signaling pathway.

Key words

apoptosis, ovarian cancer, cell proliferation, Wnt signaling pathway, miR-140-5p

References (27)

  1. Webb PM, Jordan SJ. Epidemiology of epithelial ovarian cancer. Best Pract Res Clin Obstet Gynaecol. 2017;41:3–14.
  2. Heintz APM, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. FIGO 26th Annual Report on the Results of Treatment in Gynecological Cancer. Int J Gynaecol Obstet. 2006;95(Suppl 1):S161–S192.
  3. Reid BM, Permuth JB, Sellers TA. Epidemiology of ovarian cancer: A review. Cancer Biol Med. 2017;14(1):9–32.
  4. Li W, Liu Z, Chen L, Zhou L, Yao Y. MicroRNA-23b is an independent prognostic marker and suppresses ovarian cancer progression by targeting runt-related transcription factor-2. FEBS Lett. 2014;588(9):1608–1615.
  5. Chen W, Huang L, Hao C, et al. MicroRNA-155 promotes apoptosis in SKOV3, A2780, and primary cultured ovarian cancer cells. Tumour Biol. 2016;37(7):9289–9299.
  6. Li X, Chen W, Zeng W, et al. microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of XIAP. Br J Cancer. 2017;116(1):66–76.
  7. Wang M, He Y, Shi L, Shi C. Multivariate analysis by Cox proportional hazard model on prognosis of patient with epithelial ovarian cancer. Eur J Gynaecol Oncol. 2011;32(2):171–177.
  8. Li Y, Chen Y, Li J, et al. Co-delivery of microRNA-21 antisense oligonucleotides and gemcitabine using nanomedicine for pancreatic cancer therapy. Cancer Sci. 2017;108(7):1493–1503.
  9. Li P, Sun Y, Liu Q. MicroRNA-340 induces apoptosis and inhibits metastasis of ovarian cancer cells by inactivation of NF-x03BA;B1. Cell Physiol Biochem. 2016;38(5):1915–1927.
  10. Kan Q, Su Y, Yang H. MicroRNA-335 is downregulated in papillary thyroid cancer and suppresses cancer cell growth, migration and invasion by directly targeting ZEB2. Oncol Lett. 2017;14(6):7622–7628.
  11. Liu C, Liu R, Zhang D, et al. MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes. Nat Commun. 2017;8:14270–14270.
  12. Santos JC, Lima NDS, Sarian LO, et al. Exosome-mediated breast cancer chemoresistance via miR-155 transfer. Sci Rep. 2018;8(1):829–829.
  13. Flamini V, Jiang W, Cui Y. Therapeutic role of MiR-140-5p for the treatment of non-small cell lung cancer. Anticancer Res. 2017;37(8):4319–4327.
  14. Zhai H, Fesler A, Ba Y, Wu S, Ju J. Inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy. Oncotarget. 2015;6(23):19735–19746.
  15. Yang P, Xiong J, Zuo L, Liu K, Zhang H. miR-140-5p regulates cell migration and invasion of non-small cell lung cancer cells through targeting VEGFA. Mol Med Rep. 2018;18(3):2866–2872.
  16. Dihlmann S, von Knebel Doeberitz M. Wnt/beta-catenin-pathway as a molecular target for future anti-cancer therapeutics. Int J Cancer. 2005:113(4):515–524.
  17. Fang Z, Yin S, Sun R, et al. miR-140-5p suppresses the proliferation, migration and invasion of gastric cancer by regulating YES1. Mol Cancer. 2017;16(1):139–139.
  18. Lu Y, Qin T, Li J, et al. MicroRNA-140-5p inhibits invasion and angiogenesis through targeting VEGF-A in breast cancer. Cancer Gene Ther. 2017;24(9):386–392.
  19. Su Y, Xiong J, Hu J, et al. MicroRNA-140-5p targets insulin like growth factor 2 mRNA binding protein 1 (IGF2BP1) to suppress cervical cancer growth and metastasis. Oncotarget. 2016;7(42):68397–68411.
  20. Jing P, Sa N, Xu W. miR-140-5p affects the migration and invasion of hypopharyngeal carcinoma cells by downregulating ADAM10 expression [in Chinese]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016;51(3):189–196.
  21. Yu L, Lu Y, Han X, et al. microRNA-140-5p inhibits colorectal cancer invasion and metastasis by targeting ADAMTS5 and IGFBP5. Stem Cell Res Ther. 2016;7(1):180.
  22. Li H, Guan S, Lu Y, Wang F. MiR-140-5p inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion through targeting TLR4. Biomed Pharmacother. 2017;96:208–214.
  23. Hu Y, Li Y, Wu C, et al. MicroRNA-140-5p inhibits cell proliferation and invasion by regulating VEGFA/MMP2 signaling in glioma. Tumour Biol. 2017;39(4):1010428317697558. doi:10.1177/1010428317697558.
  24. Huang CL, Liu D, Ishikawa S, et al. Wnt1 overexpression promotes tumour progression in non-small cell lung cancer. Eur J Cancer. 2008;44(17):2680–2688.
  25. Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development. J Cancer Res Clin Oncol. 2003;129(4):199–221.
  26. Duchartre Y, Kim YM, Kahn M. The Wnt signaling pathway in cancer. Crit Rev Oncol Hematol. 2016;99:141–149.
  27. Wu D, Zhang J, Lu Y, et al. miR-140-5p inhibits the proliferation and enhances the efficacy of doxorubicin to breast cancer stem cells by targeting Wnt1. Cancer Gene Ther. 2019;26(3–4):74–82.