MicroRNA‑218 inhibits the migration, epithelial‑mesenchymal transition and cancer stem cell properties of prostate cancer cells

Guan,Bing; Mu,Lijun; Zhang,Linlin; Wang,Ke; Tian,Juanhua; Xu,Shan; Wang,Xinyang; He,Dalin; Du,Yuefeng

doi:10.3892/ol.2018.8877

MicroRNA‑218 inhibits the migration, epithelial‑mesenchymal transition and cancer stem cell properties of prostate cancer cells

Authors:
- Bing Guan
- Lijun Mu
- Linlin Zhang
- Ke Wang
- Juanhua Tian
- Shan Xu
- Xinyang Wang
- Dalin He
- Yuefeng Du
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Affiliations: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: June 1, 2018 https://doi.org/10.3892/ol.2018.8877
Pages: 1821-1826

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Abstract

MicroRNA (miRNA) is a class of non‑coding single‑stranded RNA, able to regulate tumor‑associated genes via binding the 3'‑UTR of the target gene mRNA. Previous publications have demonstrated that miRNA‑218 (miR‑218) acts as a tumor‑suppressive miRNA in various types of human cancer, including prostate cancer (PCa). However, the role of miR‑218 in regulating PCa cell stemness and epithelial‑mesenchymal transition remains unknown and requires further research. In the present study, it is demonstrated that miR‑218 was downregulated in 2 PCa cell lines and could suppress cell migration, EMT and the exhibition of cancer stem cell‑like properties. The expression of GLI family zinc finger 1 (Gli1) was inhibited by miR‑218 overexpression, suggesting miR‑218‑suppression of Gli1 as a potential mechanism for the tumor‑suppressive effect of miR‑218. Overall, the results indicate that miR‑218 served a critical role in the inhibition of PCa development. This may provide new insight for elucidating the mechanisms of PCa oncogenesis and suggests that miR‑218 may be a novel therapeutic target for PCa.

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1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Egan A, Dong Y, Zhang H, Qi Y, Balk SP and Sartor O: Castration-resistant prostate cancer: Adaptive responses in the androgen axis. Cancer Treat Rev. 40:426–433. 2014. View Article : Google Scholar : PubMed/NCBI
3	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
4	Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS and Johnson JM: Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 433:769–773. 2005. View Article : Google Scholar : PubMed/NCBI
5	Guo H, Ingolia NT, Weissman JS and Bartel DP: Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 466:835–840. 2010. View Article : Google Scholar : PubMed/NCBI
6	Iorio MV and Croce CM: MicroRNAs in cancer: Small molecules with a huge impact. J Clin Oncol. 27:5848–5856. 2009. View Article : Google Scholar : PubMed/NCBI
7	Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65:7065–7070. 2005. View Article : Google Scholar : PubMed/NCBI
8	Zhang X, Tang J, Zhi X, Xie K, Wang W, Li Z, Zhu Y, Yang L, Xu H and Xu Z: miR-874 functions as a tumor suppressor by inhibiting angiogenesis through STAT3/VEGF-A pathway in gastric cancer. Oncotarget. 6:1605–1617. 2015.PubMed/NCBI
9	Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, et al: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med. 17:211–215. 2011. View Article : Google Scholar : PubMed/NCBI
10	Fu W, Tao T, Qi M, Wang L, Hu J, Li X, Xing N, Du R and Han B: MicroRNA-132/212 upregulation inhibits TGF-β-mediated epithelial-mesenchymal transition of prostate cancer cells by targeting SOX4. Prostate. 76:1560–1570. 2016. View Article : Google Scholar : PubMed/NCBI
11	Nishikawa R, Goto Y, Kojima S, Enokida H, Chiyomaru T, Kinoshita T, Sakamoto S, Fuse M, Nakagawa M, Naya Y, et al: Tumor-suppressive microRNA-29s inhibit cancer cell migration and invasion via targeting LAMC1 in prostate cancer. Int J Oncol. 45:401–410. 2014. View Article : Google Scholar : PubMed/NCBI
12	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
13	Xu X, Su B, Xie C, Wei S, Zhou Y, Liu H, Dai W, Cheng P, Wang F, Xu X and Guo C: Sonic hedgehog-Gli1 signaling pathway regulates the epithelial mesenchymal transition (EMT) by mediating a new target gene, S100A4, in pancreatic cancer cells. PLoS One. 9:e964412014. View Article : Google Scholar : PubMed/NCBI
14	Takebe N, Harris PJ, Warren RQ and Ivy SP: Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways. Nat Rev Clin Oncol. 8:97–106. 2011. View Article : Google Scholar : PubMed/NCBI
15	Clement V, Sanchez P, de Tribolet N, Radovanovic I and Ruiz i Altaba A: HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol. 17:165–172. 2007. View Article : Google Scholar : PubMed/NCBI
16	Ahmed A, Ali S and Sarkar FH: Advances in androgen receptor targeted therapy for prostate cancer. J Cell Physiol. 229:271–276. 2014. View Article : Google Scholar : PubMed/NCBI
17	Brabletz T, Jung A, Spaderna S, Hlubek F and Kirchner T: Opinion: Migrating cancer stem cells-an integrated concept of malignant tumour progression. Nat Rev Cancer. 5:744–749. 2005. View Article : Google Scholar : PubMed/NCBI
18	Deshmukh A, Deshpande K, Arfuso F, Newsholme P and Dharmarajan A: Cancer stem cell metabolism: A potential target for cancer therapy. Mol Cancer. 15:692016. View Article : Google Scholar : PubMed/NCBI
19	Colak S and Medema JP: Cancer stem cells-important players in tumor therapy resistance. FEBS J. 281:4779–4791. 2014. View Article : Google Scholar : PubMed/NCBI
20	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
21	Dave B, Mittal V, Tan NM and Chang JC: Epithelial-mesenchymal transition, cancer stem cells and treatment resistance. Breast Cancer Res. 14:2022012. View Article : Google Scholar : PubMed/NCBI
22	Miska EA: How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 15:563–568. 2005. View Article : Google Scholar : PubMed/NCBI
23	Garzon R, Marcucci G and Croce CM: Targeting microRNAs in cancer: Rationale, strategies and challenges. Nat Rev Drug Discov. 9:775–789. 2010. View Article : Google Scholar : PubMed/NCBI
24	Li X, Yu Z, Li Y, Liu S, Gao C, Hou X, Yao R and Cui L: The tumor suppressor miR-124 inhibits cell proliferation by targeting STAT3 and functions as a prognostic marker for postoperative NSCLC patients. Int J Oncol. 46:798–808. 2015. View Article : Google Scholar : PubMed/NCBI
25	Zheng Z, Ding M, Ni J, Song D, Huang J and Wang J: MiR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1. Oncol Rep. 33:1291–1299. 2015. View Article : Google Scholar : PubMed/NCBI
26	Zhou N, Fei D, Zong S, Zhang M and Yue Y: MicroRNA-138 inhibits proliferation, migration and invasion through targeting hTERT in cervical cancer. Oncol Lett. 12:3633–3639. 2016. View Article : Google Scholar : PubMed/NCBI
27	Davidson MR, Larsen JE, Yang IA, Hayward NK, Clarke BE, Duhig EE, Passmore LH, Bowman RV and Fong KM: MicroRNA-218 is deleted and downregulated in lung squamous cell carcinoma. PLoS One. 5:e125602010. View Article : Google Scholar : PubMed/NCBI
28	Yu H, Gao G, Jiang L, Guo L, Lin M, Jiao X, Jia W and Huang J: Decreased expression of miR-218 is associated with poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol. 6:2904–2911. 2013.PubMed/NCBI
29	Guan H, Wei G, Wu J, Fang D, Liao Z, Xiao H, Li M and Li Y: Down-regulation of miR-218-2 and its host gene SLIT3 cooperate to promote invasion and progression of thyroid cancer. J Clin Endocrinol Metab. 98:E1334–E1344. 2013. View Article : Google Scholar : PubMed/NCBI
30	Wang XX, Ge SJ, Wang XL, Jiang LX, Sheng MF and Ma JJ: miR-218 tissue expression level is associated with aggressive progression of gastric cancer. Genet Mol Res. 15:2016.
31	Wang HT, Liu AG, Luo DS, Zhou ZN, Lin HG, Chen RZ, He JS and Chen K: miR-218 expression in osteosarcoma tissues and its effect on cell growth in osteosarcoma cells. Asian Pac J Trop Med. 7:1000–1004. 2014. View Article : Google Scholar : PubMed/NCBI
32	Wang G, Fu Y, Liu G, Ye Y and Zhang X: miR-218 inhibits proliferation, migration, and EMT of gastric cancer cells by targeting WASF3. Oncol Res. 25:355–364. 2016. View Article : Google Scholar : PubMed/NCBI
33	Jiang Z, Song Q, Zeng R, Li J, Li J, Lin X, Chen X, Zhang J and Zheng Y: MicroRNA-218 inhibits EMT, migration and invasion by targeting SFMBT1 and DCUN1D1 in cervical cancer. Oncotarget. 7:45622–45636. 2016.PubMed/NCBI
34	Tu Y, Gao X, Li G, Fu H, Cui D, Liu H, Jin W and Zhang Y: MicroRNA-218 inhibits glioma invasion, migration, proliferation, and cancer stem-like cell self-renewal by targeting the polycomb group gene Bmi1. Cancer Res. 73:6046–6055. 2013. View Article : Google Scholar : PubMed/NCBI
35	Kogo R, How C, Chaudary N, Bruce J, Shi W, Hill RP, Zahedi P, Yip KW and Liu FF: The microRNA-218~Survivin axis regulates migration, invasion, and lymph node metastasis in cervical cancer. Oncotarget. 6:1090–1100. 2015. View Article : Google Scholar : PubMed/NCBI
36	Cheng Y, Yang X, Deng X, Zhang X, Li P, Tao J and Lu Q: MicroRNA-218 inhibits bladder cancer cell proliferation, migration, and invasion by targeting BMI-1. Tumour Biol. 36:8015–8023. 2015. View Article : Google Scholar : PubMed/NCBI
37	Li F, Gu C, Tian F, Jia Z, Meng Z, Ding Y and Yang J: MiR-218 impedes IL-6-induced prostate cancer cell proliferation and invasion via suppression of LGR4 expression. Oncol Rep. 35:2859–2865. 2016. View Article : Google Scholar : PubMed/NCBI
38	Han G, Fan M and Zhang X: MicroRNA-218 inhibits prostate cancer cell growth and promotes apoptosis by repressing TPD52 expression. Biochem Biophys Res Commun. 456:804–809. 2015. View Article : Google Scholar : PubMed/NCBI
39	Nishikawa R, Goto Y, Sakamoto S, Chiyomaru T, Enokida H, Kojima S, Kinoshita T, Yamamoto N, Nakagawa M, Naya Y, et al: Tumor-suppressive microRNA-218 inhibits cancer cell migration and invasion via targeting of LASP1 in prostate cancer. Cancer Sci. 105:802–811. 2014. View Article : Google Scholar : PubMed/NCBI
40	Inaguma S, Kasai K, Hashimoto M and Ikeda H: GLI1 modulates EMT in pancreatic cancer-letter. Cancer Res. 72:3702–3703. 3704–3705. 2012. View Article : Google Scholar : PubMed/NCBI