miR‑584 inhibits cell proliferation, migration and invasion in vitro and enhances the sensitivity to cisplatin in human cervical cancer by negatively targeting GLI1

Wang,Tingfeng; Feng,Juan; Zhang,Aiyun

doi:10.3892/etm.2020.8449

miR‑584 inhibits cell proliferation, migration and invasion in vitro and enhances the sensitivity to cisplatin in human cervical cancer by negatively targeting GLI1

Authors:
- Tingfeng Wang
- Juan Feng
- Aiyun Zhang
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Affiliations: Department of Gynaecology and Obstetrics, Weifang Maternity and Child Care Hospital, Weifang, Shandong 261042, P.R. China, Department of Gynaecology and Obstetrics, AnQiu Maternity and Child Care Hospital, Weifang, Shandong 261042, P.R. China
Published online on: January 14, 2020 https://doi.org/10.3892/etm.2020.8449
Pages: 2059-2066
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cervical cancer is the most lethal malignancy amongst women worldwide. MicroRNAs (miRNAs/miRs) play a critical role in the progression of cervical cancer. Compelling evidence indicates that miR‑584 acts as a tumor suppressor in some types of cancers. However, the function of miR‑584 in cervical cancer has not been illustrated. In the present study, the effects and mechanism of miR‑584 in the process of proliferation, migration and invasion, and drug sensitivity to cisplatin in cervical cancer were determined. miR‑584 expression decreased markedly in cervical cancer tissues and cell lines compared with healthy control samples. Dual‑luciferase reporter assays confirmed that glioma‑associated oncogene 1 (GLI1) is a novel molecular target of miR‑584. The overexpression of miR‑584 inhibited the expression of GLI1, reduced cell proliferation, migration and invasion, and induced apoptosis in HeLa cells. However, the silencing of miR‑584 in CaSki cells produced the opposite effects. In addition, the overexpression of GLI1 in HeLa‑cells overexpressing miR‑584 markedly reversed the miR‑584‑induced inhibitory effect. Flow cytometry results showed that miR‑584 enhanced cisplatin sensitivity by promoting chemotherapy‑induced apoptosis. Therefore, miR‑584 acted as a tumor suppressor miRNA and might be a novel target gene for future cervical cancer treatments.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Burki TK: Cervical cancer: Screening and risk with age. Lancet Oncol. 15:e1072014. View Article : Google Scholar : PubMed/NCBI
3	Waggoner SE: Cervical cancer. Lancet. 361:2217–2225. 2003. View Article : Google Scholar : PubMed/NCBI
4	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
5	Shen J, Stass SA and Jiang F: MicroRNAs as potential biomarkers in human solid tumors. Cancer Lett. 329:125–136. 2013. View Article : Google Scholar : PubMed/NCBI
6	Zhang Y, Wang Y and Wang J: MicroRNA-584 inhibits cell proliferation and invasion in non-small cell lung cancer by directly targeting MTDH. Exp Ther Med. 15:2203–2211. 2018.PubMed/NCBI
7	Zheng L, Chen Y, Ye L, Jiao W, Song H, Mei H, Li D, Yang F, Li H, Huang K and Tong Q: miRNA-584-3p inhibits gastric cancer progression by repressing Yin Yang 1-facilitated MMP-14 expression. Sci Rep. 7:89672017. View Article : Google Scholar : PubMed/NCBI
8	Li Q, Li Z, Wei S, Wang W, Chen Z, Zhang L, Chen L, Li B, Sun G, Xu J, et al: Overexpression of miR-584-5p inhibits proliferation and induces apoptosis by targeting WW domain-containing E3 ubiquitin protein ligase 1 in gastric cancer. J Exp Clin Cancer Res. 36:592017. View Article : Google Scholar : PubMed/NCBI
9	Orlandella FM, Di Maro G, Ugolini C, Basolo F and Salvatore G: TWIST1/miR-584/TUSC2 pathway induces resistance to apoptosis in thyroid cancer cells. Oncotarget. 7:70575–70588. 2016. View Article : Google Scholar : PubMed/NCBI
10	Xue H, Guo X, Han X, Yan S, Zhang J, Xu S, Li T, Guo X, Zhang P, Gao X, et al: MicroRNA-584-3p, a novel tumor suppressor and prognostic marker, reduces the migration and invasion of human glioma cells by targeting hypoxia-induced ROCK1. Oncotarget. 7:4785–4805. 2016. View Article : Google Scholar : PubMed/NCBI
11	Xiang J, Wu Y, Li DS, Wang ZY, Shen Q, Sun TQ, Guan Q and Wang YJ: miR-584 suppresses invasion and cell migration of thyroid carcinoma by regulating the target oncogene ROCK1. Oncol Res Treat. 38:436–440. 2015. View Article : Google Scholar : PubMed/NCBI
12	Wang XP, Deng XL and Li LY: MicroRNA-584 functions as a tumor suppressor and targets PTTG1IP in glioma. Int J Clin Exp Pathol. 7:8573–8582. 2014.PubMed/NCBI
13	Ueno K, Hirata H, Shahryari V, Chen Y, Zaman MS, Singh K, Tabatabai ZL, Hinoda Y and Dahiya R: Tumor suppressor microRNA-584 directly targets oncogene Rock-1 and decreases invasion ability in human clear cell renal cell carcinoma. Br J Cancer. 104:308–315. 2011. View Article : Google Scholar : PubMed/NCBI
14	Wang L, Wang B, Fang M, Guo F and Cui M: Identification of microRNAs and target genes involved in serous ovarian carcinoma and their influence on survival. Eur J Gynaecol Oncol. 35:655–661. 2014.PubMed/NCBI
15	Didiasova M, Schaefer L and Wygrecka M: Targeting GLI transcription factors in cancer. Molecules. 23(pii): E10032018. View Article : Google Scholar : PubMed/NCBI
16	Mastrangelo E and Milani M: Role and inhibition of GLI1 protein in cancer. Lung Cancer. 9:35–43. 2018.PubMed/NCBI
17	Zhao D and Cui Z: MicroRNA-361-3p regulates retinoblastoma cell proliferation and stemness by targeting hedgehog signaling. Exp Ther Med. 17:1154–1162. 2019.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 : PubMed/NCBI
19	Hasanzadeh M, Movahedi M, Rejali M, Maleki F, Moetamani-Ahmadi M, Seifi S, Hosseini Z, Khazaei M, Amerizadeh F, Ferns GA, et al: The potential prognostic and therapeutic application of tissue and circulating microRNAs in cervical cancer. J Cell Physiol. 234:1289–1294. 2019. View Article : Google Scholar : PubMed/NCBI
20	Shenouda SK and Alahari SK: MicroRNA function in cancer: Oncogene or a tumor suppressor? Cancer Metastasis Rev. 28:369–378. 2009. View Article : Google Scholar : PubMed/NCBI
21	Abdelfattah N, Rajamanickam S, Panneerdoss S, Timilsina S, Yadav P, Onyeagucha BC, Garcia M, Vadlamudi R, Chen Y, Brenner A, et al: MiR-584-5p potentiates vincristine and radiation response by inducing spindle defects and DNA damage in medulloblastoma. Nat Commun. 9:45412018. View Article : Google Scholar : PubMed/NCBI
22	Sabol M, Trnski D, Musani V, Ozretic P and Levanat S: Role of GLI transcription factors in pathogenesis and their potential as new therapeutic targets. Int J Mol Sci. 19(pii): E25622018. View Article : Google Scholar : PubMed/NCBI
23	Skoda AM, Simovic D, Karin V, Kardum V, Vranic S and Serman L: The role of the Hedgehog signaling pathway in cancer: A comprehensive review. Bosn J Basic Med Sci. 18:8–20. 2018. View Article : Google Scholar : PubMed/NCBI
24	Chaudary N, Pintilie M, Hedley D, Fyles AW, Milosevic M, Clarke B, Hill RP and Mackay H: Hedgehog pathway signaling in cervical carcinoma and outcome after chemoradiation. Cancer. 118:3105–3115. 2012. View Article : Google Scholar : PubMed/NCBI
25	Çalışkan M, Güler H and Bozok Çetintaş V: Current updates on microRNAs as regulators of chemoresistance. Biomed Pharmacother. 95:1000–1012. 2017. View Article : Google Scholar : PubMed/NCBI