MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells Retraction in /10.3892/ijmm.2024.5348

Chen,Xu; Cao,Ruiqin; Liu,Haifang; Zhang,Tuanying; Yuan,Xinrong; Xu,Shuxiang

doi:10.3892/ijmm.2020.4704

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

Retraction in: /10.3892/ijmm.2024.5348

Authors:
- Xu Chen
- Ruiqin Cao
- Haifang Liu
- Tuanying Zhang
- Xinrong Yuan
- Shuxiang Xu
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Affiliations: Department of Obstetrics and Gynaecology, Huashan Hospital North, Fudan University, Shanghai 200040, P.R. China, Department of Obstetrics and Gynaecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, P.R. China, Department of Obstetrics and Gynaecology, No.1 Hospital of Naval Force of Southern Theater Command, PLA, Zhanjiang, Guangdong 524005, P.R. China
Published online on: August 12, 2020 https://doi.org/10.3892/ijmm.2020.4704
Pages: 1301-1310
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs) have been reported to have important regulatory roles in the progression of several types of cancer, including cervical cancer (CC). However, the biological roles and regulatory mechanisms of miRNAs in CC remain to be fully elucidated. The aim of the present study was to examine the functions of miRNAs in CC and the possible mechanisms. Using a microarray, it was identified that miRNA‑15a‑5p (miR‑15a‑5p) was one of the most downregulated miRNAs in CC tissues compared with adjacent noncancerous tissues. The low expression of miR‑15a‑5p was observed in CC tumor tissues with distant metastasis and in CC cell lines. In addition, the effects of miR‑15a‑5p upregulation on cell viability, apoptosis, invasion and migration of CC cells were investigated using CCK‑8, flow cytometry, Transwell and wound healing assays, respectively. It was demonstrated that upregulation of miR‑15a‑5p significantly suppressed the viability, migration and invasion, and promoted the apoptosis of SiHa and C‑33A cells. Furthermore, yes‑associated protein 1 (YAP1), a well‑known oncogene, was confirmed to be directly targeted by miR‑15a‑5p and was found to be negatively regulated by miR‑15a‑5p. Further correlation analysis indicated that miR‑15a‑5p expression was negatively correlated with YAP1 expression in CC tissues. Notably, overexpression of YAP1 abrogated the tumor suppressive effects of miR‑15a‑5p in CC cells. Taken together, these present findings indicated that the miR‑15a‑5p/YAP1 axis may provide a novel strategy for the clinical treatment of CC.

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1	Alldredge JK and Tewari KS: Clinical trials of antiangiogenesis therapy in recurrent/persistent and metastatic cervical cancer. oncologist. 21:576–585. 2016. View Article : Google Scholar : PubMed/NCBI
2	Tsikouras P, Zervoudis S, Manav B, Tomara E, Iatrakis G, Romanidis C, Bothou A and Galazios G: Cervical cancer: Screening, diagnosis and staging. J BUON. 21:320–325. 2016.PubMed/NCBI
3	Fang J, Zhang H and Jin S: Epigenetics and cervical cancer: From pathogenesis to therapy. Tumour Biol. 35:5083–5093. 2014. View Article : Google Scholar : PubMed/NCBI
4	Wang J, Liu Y, Wang X, Li J, We J, Wang Y, Song W and Zhang Z: MiR-1266 promotes cell proliferation, migration and invasion in cervical cancer by targeting DAB2IP. Biochim Biophys Acta Mol Basis Dis. 1864:3623–3630. 2018. View Article : Google Scholar : PubMed/NCBI
5	Zhu L, Zhu L, Shi H, Wang H, Yan J, Liu B, Chen W, He J, Zhou Z, Yang X and Liu T: Evaluating early response of cervical cancer under concurrent chemo-radiotherapy by intravoxel incoherent motion MR imaging. BMC Cancer. 16:792016. View Article : Google Scholar : PubMed/NCBI
6	Li T and Cho WC: MicroRNAs: Mechanisms, functions and progress. Genomics Proteomics Bioinformatics. 10:237–238. 2012. View Article : Google Scholar : PubMed/NCBI
7	Shukla GC, Singh J and Barik S: MicroRNAs: Processing, Maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 3:83–92. 2011.PubMed/NCBI
8	Zhu H, Xie R, Liu X, Shou J, Gu W, Gu S and Che X: MicroRNA-494 improves functional recovery and inhibits apoptosis by modulating PTEN/AKT/mTOR pathway in rats after spinal cord injury. Biomed Pharmacother. 92:879–887. 2017. View Article : Google Scholar : PubMed/NCBI
9	Zhu Y, Wu G, Yan W, Zhan H and Sun P: miR-146b-5p regulates cell growth, invasion, and metabolism by targeting PDHB in colorectal cancer. Am J Cancer Res. 7:1136–1150. 2017.PubMed/NCBI
10	Li JH, Zhang Z, Du MZ, Guan YC, Yao JN, Yu HY, Wang BJ, Wang XL, Wu SL and Li Z: microRNA-141-3p fosters the growth, invasion, and tumorigenesis of cervical cancer cells by targeting FOXA2. Arch Biochem Biophys. 657:23–30. 2018. View Article : Google Scholar : PubMed/NCBI
11	Xia P, Gao X, Duan L, Zhang W and Sun YF: Mulberrin (Mul) reduces spinal cord injury (SCI)-induced apoptosis, inflammation and oxidative stress in rats via miroRNA-337 by targeting Nrf-2. Biomed Pharmacother. 107:1480–1487. 2018. View Article : Google Scholar : PubMed/NCBI
12	Yang Y, Liu Y, Li G, Li L, Geng P and Song H: microRNA-214 suppresses the growth of cervical cancer cells by targeting EZH2. Oncol Lett. 16:5679–5686. 2018.PubMed/NCBI
13	Dong J, Wang M, Ni D, Zhang L, Wang W, Cui X, Fu S and Yao S: MicroRNA-217 functions as a tumor suppressor in cervical cancer cells through targeting Rho-associated protein kinase 1. Oncol Lett. 16:5535–5542. 2018.PubMed/NCBI
14	Chen Y, Song Y, Mi Y, Jin H, Cao J, Li H, Han L, Huang T, Zhang X, Ren S, et al: microRNA-499a promotes the progression and chemoresistance of cervical cancer cells by targeting SOX6. Apoptosis. 25:205–216. 2020. View Article : Google Scholar : PubMed/NCBI
15	Yang D and Zhang Q: miR-152 may function as an early diagnostic and prognostic biomarker in patients with cervical intraepithelial neoplasia and patients with cervical cancer. Oncol Lett. 17:5693–5698. 2019.PubMed/NCBI
16	Guo Y, Ma D, Jia SF, Liu J, Fan SB, Zhang M, Shi LR, Jiang LL, Shi JX, Wang HQ, et al: Proliferation of MicroRNA-365 and E74-like factor 4 in cervical cancer cells and its clinical significance. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 41:220–227. 2019.PubMed/NCBI
17	Mei LL, Wang WJ, Qiu YT, Xie XF, Bai J and Shi ZZ: miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma. PLoS One. 12:e01856362017. View Article : Google Scholar : PubMed/NCBI
18	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
19	Zhang MY, Lin J and Kui YC: MicroRNA-345 suppresses cell invasion and migration in non-small cell lung cancer by directly targeting YAP1. Eur Rev Med Pharmacol Sci. 23:2436–2443. 2019.PubMed/NCBI
20	Wang ZM, Wan XH, Sang GY, Zhao JD, Zhu QY and Wang DM: miR-15a-5p suppresses endometrial cancer cell growth via Wnt/β-catenin signaling pathway by inhibiting WNT3A. Eur Rev Med Pharmacol Sci. 21:4810–4818. 2017.PubMed/NCBI
21	Chen D, Wu D, Shao K, Ye B, Huang J and Gao Y: MiR-15a-5p negatively regulates cell survival and metastasis by targeting CXCL10 in chronic myeloid leukemia. Am J Transl Res. 9:4308–4316. 2017.PubMed/NCBI
22	Huang X, Tang F, Weng Z, Zhou M and Zhang Q: MiR-591 functions as tumor suppressor in breast cancer by targeting TCF4 and inhibits Hippo-YAP/TAZ signaling pathway. Cancer Cell Int. 19:1082019. View Article : Google Scholar : PubMed/NCBI
23	Zender L, Spector MS, Xue W, Flemming P, Cordon-Cardo C, Silke J, Fan ST, Luk JM, Wigler M, Hannon GJ, et al: Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach. Cell. 125:1253–1267. 2006. View Article : Google Scholar : PubMed/NCBI
24	Laengsri V, Kerdpin U, Plabplueng C, Treeratanapiboon L and Nuchnoi P, Treeratanapiboon L and Nuchnoi P: Cervical cancer markers: Epigenetics and microRNAs. Lab Med. 49:97–111. 2018. View Article : Google Scholar : PubMed/NCBI
25	Satapathy S, Batra J, Jeet V, Thompson EW and Punyadeera C: MicroRNAs in HPV associated cancers: Small players with big consequences. Expert Rev Mol Diagn. 17:711–722. 2017. View Article : Google Scholar : PubMed/NCBI
26	Xia N, Tan WF, Peng QZ and Cai HN: MiR-374b reduces cell proliferation and cell invasion of cervical cancer through regulating FOXM1. Eur Rev Med Pharmacol Sci. 23:513–521. 2019.PubMed/NCBI
27	Yao R, Zheng H, Wu L and Cai P: miRNA-641 inhibits the proliferation, migration, and invasion and induces apoptosis of cervical cancer cells by directly targeting ZEB1. Onco Targets Ther. 11:8965–8976. 2018. View Article : Google Scholar :
28	Xu Y, He Q, Lu Y, Tao F, Zhao L and Ou R: MicroRNA-218-5p inhibits cell growth and metastasis in cervical cancer via LYN/NF-κB signaling pathway. Cancer Cell Int. 18:1982018. View Article : Google Scholar
29	Yuan M, Zhao S, Chen R, Wang G, Bie Y, Wu Q and Cheng J: MicroRNA-138 inhibits tumor growth and enhances chemosensitivity in human cervical cancer by targeting H2AX. Exp Ther Med. 19:630–638. 2020.
30	Ergun S, Güney S, Temiz E, Petrovic N and Gunes S: Significance of miR-15a-5p and CNKSR3 as novel prognostic biomarkers in non-small cell lung cancer. Anticancer Agents Med Chem. 18:1695–1701. 2018. View Article : Google Scholar : PubMed/NCBI
31	Gao D, Zhang Y, Zhu M, Liu S and Wang X: miRNA expression profiles of HPV-infected patients with cervical cancer in the uyghur population in China. PLoS One. 11:e01647012016. View Article : Google Scholar : PubMed/NCBI
32	Miao H, Wang N, Shi LX, Wang Z and Song WB: Overexpression of mircoRNA-137 inhibits cervical cancer cell invasion, migration and epithelial-mesenchymal transition by suppressing the TGF-β/smad pathway via binding to GREM1. Cancer Cell Int. 19:1472019. View Article : Google Scholar
33	Wu Y, Huang J, Xu H and Gong Z: Over-expression of miR-15a-3p enhances the radiosensitivity of cervical cancer by targeting tumor protein D52. Biomed Pharmacother. 105:1325–1334. 2018. View Article : Google Scholar : PubMed/NCBI
34	Druz A, Chen YC, Guha R, Betenbaugh M, Martin SE and Shiloach J: Large-scale screening identifies a novel microRNA, miR-15a-3p which induces apoptosis in human cancer cell lines. RNA Biol. 10:287–300. 2013. View Article : Google Scholar : PubMed/NCBI
35	He J: Knocking down MiR-15a expression promotes the occur-rence and development and induces the EMT of NSCLC cells in vitro. Saudi J Biol Sci. 24:1859–1865. 2017. View Article : Google Scholar
36	Bonci D, Coppola V, Musumeci M, Addario A, Giuffrida R, Memeo L, D'Urso L, Pagliuca A, Biffoni M, Labbaye C, et al: The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities. Nat Med. 14:1271–1277. 2008. View Article : Google Scholar : PubMed/NCBI
37	Luo Q, Li X, Li J, Kong X, Zhang J, Chen L, Huang Y and Fang L: MiR-15a is underexpressed and inhibits the cell cycle by targeting CCNE1 in breast cancer. Int J Oncol. 43:1212–1218. 2013. View Article : Google Scholar : PubMed/NCBI
38	Wu C, Zheng X, Li X, Fesler A, Hu W, Chen L, Xu B, Wang Q, Tong A, Burke S, et al: Reduction of gastric cancer proliferation and invasion by miR-15a mediated suppression of Bmi-1 translation. Oncotarget. 7:14522–14536. 2016. View Article : Google Scholar : PubMed/NCBI
39	Guo S, Xu X, Tang Y, Zhang C, Li J, Ouyang Y, Ju J, Bie P and Wang H: miR-15a inhibits cell proliferation and epithelial to mesenchymal transition in pancreatic ductal adenocarcinoma by down-regulating Bmi-1 expression. Cancer Lett. 344:40–46. 2014. View Article : Google Scholar
40	Wang Z, Liu P, Zhou X, Wang T, Feng X, Sun YP, Xiong Y, Yuan HX and Guan KL: Endothelin promotes colorectal tumorigenesis by activating YAP/TAZ. Cancer Res. 77:2413–2423. 2017. View Article : Google Scholar : PubMed/NCBI
41	Li N, Yu N, Wang J, Xi H, Lu W, Xu H, Deng M, Zheng G and Liu H: miR-222/VGLL4/YAP-TEAD1 regulatory loop promotes proliferation and invasion of gastric cancer cells. Am J Cancer Res. 5:1158–1168. 2015.PubMed/NCBI
42	Shao DD, Xue W, Krall EB, Bhutkar A, Piccioni F, Wang X, Schinzel AC, Sood S, Rosenbluh J, Kim JW, et al: KRAS and YAP1 converge to regulate EMT and tumor survival. Cell. 158:171–184. 2014. View Article : Google Scholar : PubMed/NCBI
43	Lee KW, Lee SS, Kim SB, Sohn BH, Lee HS, Jang HJ, Park YY, Kopetz S, Kim SS, Oh SC and Lee JS: Significant association of oncogene YAP1 with poor prognosis and cetuximab resistance in colorectal cancer patients. Clin Cancer Res. 21:357–364. 2015. View Article : Google Scholar :
44	Liu R, Huang S, Lei Y, Zhang T, Wang K, Liu B, Nice EC, Xiang R, Xie K, Li J and Huang C: FGF8 promotes colorectal cancer growth and metastasis by activating YAP1. Oncotarget. 6:935–952. 2015. View Article : Google Scholar :
45	Yu FX, Zhao B and Guan KL: Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell. 163:811–828. 2015. View Article : Google Scholar : PubMed/NCBI
46	Kang W, Tong JH, Lung RW, Dong Y, Zhao J, Liang Q, Zhang L, Pan Y, Yang W, Pang JC, et al: Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma. Mol Cancer. 14:522015. View Article : Google Scholar : PubMed/NCBI
47	Fesler A, Liu H and Ju J: Modified miR-15a has therapeutic potential for improving treatment of advanced stage colorectal cancer through inhibition of BCL2, BMI1, YAP1 and DCLK1. Oncotarget. 9:2367–2383. 2017. View Article : Google Scholar