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MiR-301a Promotes Cell Proliferation by Repressing PTEN in Renal Cell Carcinoma

Authors Li J, Jiang D, Zhang Q, Peng S, Liao G, Yang X, Tang J, Xiong H, Pang J

Received 11 March 2020

Accepted for publication 30 May 2020

Published 10 June 2020 Volume 2020:12 Pages 4309—4320

DOI https://doi.org/10.2147/CMAR.S253533

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li


Jun Li,1,* Donggen Jiang,1,* Qian Zhang,2,* Shubin Peng,3 Guolong Liao,1 Xiangwei Yang,1 Jiani Tang,1 Haiyun Xiong,1 Jun Pang1

1Department of Urology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, People’s Republic of China; 2Department of Rehabilitation Medicine, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, People’s Republic of China; 3Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jun Pang; Haiyun Xiong
Department of Urology, Seventh Affiliated Hospital, Sun Yat-Sen University, 628 Zhenyuan Road, Shenzhen 518107, People’s Republic of China
Tel +86-18802044177
; +86-18922869986
Email pangjun2@mail.sysu.edu.cn; xionghy7@mail.sysu.edu.cn

Objective: Renal cell carcinoma (RCC) displays an increasing incidence and mortality rate worldwide in recent years. More and more evidence demonstrated microRNAs function as positive or negative regulatory factors in many cancers, while the role of miR-301a in RCC is still unclear.
Material and Methods: The expression and clinical significance of miR-301a were assessed via bioinformatic software on open microarray datasets of the Cancer Genome Atlas (TCGA) and then confirmed by quantitative real-time PCR (qRT-PCR) in RCC cell lines. Loss of function assays were performed in RCC cell lines both in vitro and in vivo. Cell Counting Kit-8 (CCK-8), flow cytometry, luciferase reporter assays, Western blotting, and immunohistochemistry were employed to explore the mechanisms of the effect of miR-301a on RCC.
Results: By analyzing RCC clinical specimens and cell lines, we found a uniform increased miR-301a in expression in comparison with normal renal tissue or normal human proximal tubule epithelial cell line (HK-2). In addition, miR-301a upregulation correlated advanced stage and poor prognosis of clear cell RCC (ccRCC). Anti-miR-301a could inhibit growth and cell cycle G1/S transition in RCC cell lines. Moreover, we found that PTEN was identified as a direct target of miR-301a that might partially interrupt miR-301a-induced G1/S transition. Importantly, nude-mouse models revealed that knockdown of miR-301a delayed tumor growth.
Conclusion: These results indicate that miR-301a functions as a tumor-promoting miRNA through regulating PTEN expression, representing a novel therapeutic target for RCC.

Keywords: miR-301a, PTEN, renal cell carcinoma, proliferation, G1/S transition

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