Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

MiR-557 downregulation lowered cell proliferation and malignancy in glioblastoma by targeting ADAM17

Zongping Li¹, Hongyuan Liu¹, Zhi Tang² , Qi Zhong¹, Xu Yang¹, Ye Zhang¹, Pengcheng He¹, Xiaoyi Wang¹

¹Department of Neurosurgery, Mianyang Central Hospital, Mianyang City; ²Department of Neurosurgery, Yanting County People’s Hospital, Mianyang City, Sichuan Province 621600, China.

For correspondence:- Zhi Tang Email: tangzhi77896@126.com Tel:+868167227180

Accepted: 27 January 2021 Published: 28 February 2021

Citation: Li Z, Liu H, Tang Z, Zhong Q, Yang X, Zhang Y, et al. MiR-557 downregulation lowered cell proliferation and malignancy in glioblastoma by targeting ADAM17. Trop J Pharm Res 2021; 20(2):257-262 doi: 10.4314/tjpr.v20i2.5

© 2021 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To examine the role of miR-557 in the pathogenesis and development of glioblastoma (GBM) and its potential regulatory mechanism.

Methods: Dysregulation of miR-557 in GBM cells was determined using quantitative (real-time) PCR (qPCR). Cell proliferative ability, migratory activity and invasive ability were measured using the MTT colorimetric assay, wound healing assay and Transwell chambers assay. The direct target mRNA of miR-557 was predicted, and further validated using TargetScan and luciferase assay, respectively.

Results: Compared with human astrocytes (HAs), the downregulation of miR-557 was observed in human GBM cell lines. In U-251MG and A172 cells that overexpressed miR-557 mimics, the level of proliferation was significantly reduced, the wound width was larger, and the number of invaded cells wan decreased than that of NC mimics. Predictive results from TargetScan and results of luciferase assay demonstrated that miR-557 directly targets the 3’-untranslated region (3’-UTR) of ADAM17. In A172 cells and U-251MG cells, the upregulation E-cadherin (E-cad) and the downregulation of N-cadherin (N-cad) and vimentin (Vim) were caused by miR-557 mimics as compared with NC mimics. expression of ADAM17, NICD, HES1, and EGFR was downregulated by miR-557 mimics and upregulated by miR-557 inhibitors in A172 cells and U-251MG cells.

Conclusion: Downregulation of miR-557 accelerates GBM cell growth and malignancy by directly targeting ADAM17 3’-UTR, providing a prognostic and potential therapeutic factor for new drug discovery in GBM.

Keywords: MiR-557, Cell proliferation, Malignancy, Glioblastoma cells, ADAM17