MicroRNA‑217 functions as a tumor suppressor in cervical cancer cells through targeting Rho‑associated protein kinase 1

Dong,Jing; Wang,Maoxiu; Ni,Donghua; Zhang,Lixin; Wang,Wen; Cui,Xiujuan; Fu,Shijie; Yao,Shujuan

doi:10.3892/ol.2018.9335

MicroRNA‑217 functions as a tumor suppressor in cervical cancer cells through targeting Rho‑associated protein kinase 1

Authors:
- Jing Dong
- Maoxiu Wang
- Donghua Ni
- Lixin Zhang
- Wen Wang
- Xiujuan Cui
- Shijie Fu
- Shujuan Yao
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Jining Medical University Affiliated Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China, Deparment of Clinical Medicine, Anhui Medical University, Meishan Road, Hefei, Anhui 230032, P.R. China
Published online on: August 20, 2018 https://doi.org/10.3892/ol.2018.9335
Pages: 5535-5542
Copyright: © Dong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The abnormal expression of microRNAs (miRNAs/miRs) has been widely reported in various tumor types. miR‑217 was demonstrated to be aberrantly expressed in a number of tumors, including pancreatic adenocarcinoma and osteosarcoma; however, its specific expression pattern has never been investigated in cervical cancer cells. Compared with normal control, the level of Rho‑associated protein kinase 1 (ROCK1) expression was markedly increased in cervical cancer tissues and cells compared with that in non‑cancerous tissues and cells. The expression of miR‑217 was significantly reduced in cervical cancer tissues and cell lines. Overexpression of miR‑217 could suppress colony formation and the cell invasion capacity of SiHa and HeLa cells. Flow cytometry indicated that miR‑217 significantly increased cell apoptosis in SiHa and HeLa cells. Dual‑luciferase reporter assays demonstrated that ROCK1 was a target gene of miR‑217. In addition, overexpression of ROCK1 also led to an increased invasion capacity in SiHa cells, even when miR‑217 was inhibited, indicating that the anti‑invasive effects of miR‑217 were mediated through ROCK1. In summary, the results of the present study indicated that miR‑217 functions as a tumor suppressor in cervical cancer cells, primarily by targeting ROCK1.

View Figures

View References

1	Song J and Li Y: miR-25-3p reverses epithelial-mesenchymal transition via targeting Sema4C in cisplatin-resistance cervical cancer cells. Cancer Sci. 108:13–31. 2016.
2	Yi Y, Li H, Lv Q, Wu K and Zhang W, Zhang J, Zhu D, Liu Q and Zhang W: miR-202 inhibits the progression of human cervical cancer through inhibition of cyclin D1. Oncotarget. 7:72067–72075. 2016. View Article : Google Scholar : PubMed/NCBI
3	Azizmohammadi S, Safari A, Azizmohammadi S, Kaghazian M, Sadrkhanlo M, Yahaghi E, Farshgar R and Seifoleslami M: Molecular identification of miR-145 and miR-9 expression level as prognostic biomarkers for early-stage cervical cancer detection. QJM. 110:11–15. 2017. View Article : Google Scholar : PubMed/NCBI
4	Chandrasekaran KS, Sathyanarayanan A and Karunagaran D: Downregulation of HMGB1 by miR-34a is sufficient to suppress proliferation, migration and invasion of human cervical and colorectal cancer cells. Tumour Biol. 37:13155–13166. 2016. View Article : Google Scholar : PubMed/NCBI
5	Cong J, Liu R, Wang X, Jiang H and Zhang Y: MiR-634 decreases cell proliferation and induces apoptosis by targeting mTOR signaling pathway in cervical cancer cells. Artif Cells Nanomed Biotechnol. 44:1694–1701. 2016. View Article : Google Scholar : PubMed/NCBI
6	Deng Y, Xiong Y and Liu Y: miR-376c inhibits cervical cancer cell proliferation and invasion by targeting BMI1. Int J Exp Pathol. 97:257–265. 2016. View Article : Google Scholar : PubMed/NCBI
7	Fan Z, Cui H, Yu H, Ji Q, Kang L, Han B, Wang J, Dong Q, Li Y, Yan Z, et al: MiR-125a promotes paclitaxel sensitivity in cervical cancer through altering STAT3 expression. Oncogenesis. 5:e2232016. View Article : Google Scholar : PubMed/NCBI
8	Fang W, Shu S, Yongmei L, Endong Z, Lirong Y and Bei S: miR-224-3p inhibits autophagy in cervical cancer cells by targeting FIP200. Sci Rep. 6:332292016. View Article : Google Scholar : PubMed/NCBI
9	Huang P, Xi J and Liu S: MiR-139-3p induces cell apoptosis and inhibits metastasis of cervical cancer by targeting NOB1. Biomed Pharmacother. 83:850–856. 2016. View Article : Google Scholar : PubMed/NCBI
10	Xia D, Li X, Niu Q, Liu X, Xu W, Ma C, Gu H, Liu Z, Shi L, Tian X, et al: MicroRNA-185 suppresses pancreatic cell proliferation by targeting transcriptional coactivator with PDZ-binding motif in pancreatic cancer. Exp Ther Med. 15:657–666. 2018.PubMed/NCBI
11	Zhu X, Ju S, Yuan F, Chen G, Shu Y, Li C, Xu Y, Luo J and Xia L: microRNA-664 enhances proliferation, migration and invasion of lung cancer cells. Exp Ther Med. 13:3555–3562. 2017. View Article : Google Scholar : PubMed/NCBI
12	Cheng X, Chen J and Huang Z: miR-372 promotes breast cancer cell proliferation by directly targeting LATS2. Exp Ther Med. 15:2812–2817. 2018.PubMed/NCBI
13	Zheng F, Zhang J, Luo S, Yi J, Wang P, Zheng Q and Wen Y: miR-143 is associated with proliferation and apoptosis involving ERK5 in HeLa cells. Oncol Lett. 12:3021–3027. 2016. View Article : Google Scholar : PubMed/NCBI
14	Azam AT, Bahador R, Hesarikia H, Shakeri M and Yeganeh A: Downregulation of microRNA-217 and microRNA-646 acts as potential predictor biomarkers in progression, metastasis, and unfavorable prognosis of human osteosarcoma. Tumour Biol. 37:5769–5773. 2016. View Article : Google Scholar : PubMed/NCBI
15	Popov A, Szabo A and Mandys V: Small nucleolar RNA U91 is a new internal control for accurate microRNAs quantification in pancreatic cancer. BMC Cancer. 15:7742015. View Article : Google Scholar : PubMed/NCBI
16	Zhou L, Xu Z, Ren X, Chen K and Xin S: MicroRNA-124 (MiR-124) inhibits cell proliferation, metastasis and invasion in colorectal cancer by downregulating Rho-associated protein kinase 1 (ROCK1). Cell Physiol Biochem. 38:1785–1795. 2016. View Article : Google Scholar : PubMed/NCBI
17	Xu B, Huang Y, Niu X, Tao T, Jiang L, Tong N, Chen S, Liu N, Zhu W and Chen M: Hsa-miR-146a-5p modulates androgen-independent prostate cancer cells apoptosis by targeting ROCK1. Prostate. 75:1896–1903. 2015. View Article : Google Scholar : PubMed/NCBI
18	Hu CB, Li QL, Hu JF, Zhang Q, Xie JP and Deng L: miR-124 inhibits growth and invasion of gastric cancer by targeting ROCK1. Asian Pac J Cancer Prev. 15:6543–6546. 2014. View Article : Google Scholar : PubMed/NCBI
19	Li J, Song Y, Wang Y, Luo J and Yu W: MicroRNA-148a suppresses epithelial-to-mesenchymal transition by targeting ROCK1 in non-small cell lung cancer cells. Mol Cell Biochem. 380:277–282. 2013. View Article : Google Scholar : PubMed/NCBI
20	Shin JY, Kim YI, Cho SJ, Lee MK, Kook MC, Lee JH, Lee SS, Ashktorab H, Smoot DT, Ryu KW, et al: MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer. PLoS One. 9:e852052014. View Article : Google Scholar : PubMed/NCBI
21	Wan X, Cheng Q, Peng R, Ma Z, Chen Z, Cao Y and Jiang B: ROCK1, a novel target of miR-145, promotes glioma cell invasion. Mol Med Rep. 9:1877–1882. 2014. View Article : Google Scholar : PubMed/NCBI
22	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 : PubMed/NCBI
23	Hwang HW and Mendell JT: MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 96 Suppl:S40–S44. 2007.
24	Gandellini P, Giovannetti E and Nicassio F: MicroRNAs in cancer management: Big challenges for small molecules. Biomed Res Int. 2015:9821562015. View Article : Google Scholar : PubMed/NCBI
25	Li GB, Cheng Q, Liu L, Zhou T, Shan CY, Hu XY, Zhou J, Liu EH, Li P and Gao N: Mitochondrial translocation of cofilin is required for allyl isothiocyanate-mediated cell death via ROCK1/PTEN/PI3K signaling pathway. Cell Commun Signal. 11:502013. View Article : Google Scholar : PubMed/NCBI
26	Narumiya S, Tanji M and Ishizaki T: Rho signaling, ROCK and mDia1, in transformation, metastasis and invasion. Cancer Metastasis Rev. 28:65–76. 2009. View Article : Google Scholar : PubMed/NCBI
27	Matsubara M and Bissell MJ: Inhibitors of Rho kinase (ROCK) signaling revert the malignant phenotype of breast cancer cells in 3D context. Oncotarget. 7:31602–31622. 2016. View Article : Google Scholar : PubMed/NCBI
28	Liu S: The ROCK signaling and breast cancer metastasis. Mol Biol Rep. 38:1363–1366. 2011. View Article : Google Scholar : PubMed/NCBI
29	Xu X, Li S, Lin Y, Chen H, Hu Z, Mao Y, Xu X, Wu J, Zhu Y, Zheng X, et al: MicroRNA-124-3p inhibits cell migration and invasion in bladder cancer cells by targeting ROCK1. J Transl Med. 11:2762013. View Article : Google Scholar : PubMed/NCBI
30	Schmidt LJ, Duncan K, Yadav N, Regan KM, Verone AR, Lohse CM, Pop EA, Attwood K, Wilding G, Mohler JL, et al: RhoA as a mediator of clinically relevant androgen action in prostate cancer cells. Mol Endocrinol. 26:716–735. 2012. View Article : Google Scholar : PubMed/NCBI
31	Reymond N, Im JH, Garg R, Cox S, Soyer M, Riou P, Colomba A, Muschel RJ and Ridley AJ: RhoC and ROCKs regulate cancer cell interactions with endothelial cells. Mol Oncol. 9:1043–1055. 2015. View Article : Google Scholar : PubMed/NCBI
32	Karius T, Schnekenburger M, Dicato M and Diederich M: MicroRNAs in cancer management and their modulation by dietary agents. Biochem Pharmacol. 83:1591–1601. 2012. View Article : Google Scholar : PubMed/NCBI
33	Kong YW, Ferland-McCollough D, Jackson TJ and Bushell M: microRNAs in cancer management. Lancet Oncol. 13:e249–e258. 2012. View Article : Google Scholar : PubMed/NCBI
34	Lowery AJ, Miller N, McNeill RE and Kerin MJ: MicroRNAs as prognostic indicators and therapeutic targets: Potential effect on breast cancer management. Clin Cancer Res. 14:360–365. 2008. View Article : Google Scholar : PubMed/NCBI
35	Tufman A, Tian F and Huber RM: Can microRNAs improve the management of lung cancer patients? A clinician's perspective. Theranostics. 3:953–963. 2013. View Article : Google Scholar : PubMed/NCBI
36	Liang LH and He XH: Macro-management of microRNAs in cell cycle progression of tumor cells and its implications in anti-cancer therapy. Acta Pharmacol Sin. 32:1311–1320. 2011. View Article : Google Scholar : PubMed/NCBI
37	Chen R, Cheng Y, Zhang Y, Li Z and Geng L: RhoC mediates invasion and migration of CaSki cells through the Rho-associated serine-threonine protein kinase 1 signaling pathway. Int J Gynecol Cancer. 24:184–191. 2014. View Article : Google Scholar : PubMed/NCBI