Back to Journals » Cancer Management and Research » Volume 12

MiR-218-5p Suppresses the Progression of Retinoblastoma Through Targeting NACC1 and Inhibiting the AKT/mTOR Signaling Pathway

Authors Li L, Yu H, Ren Q

Received 15 January 2020

Accepted for publication 17 June 2020

Published 6 August 2020 Volume 2020:12 Pages 6959—6967

DOI https://doi.org/10.2147/CMAR.S246142

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Ahmet Emre Eskazan


Li Li, Hua Yu, Qian Ren

Department of Ophthalmology, The First Hospital of Shijiazhuang, Shijiazhuang, Hebei, People’s Republic of China

Correspondence: Qian Ren
Department of Ophthalmology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Shijiazhuang, Hebei, People’s Republic of China
Email liliyk@aliyun.com

Introduction: MicroRNA-218-5p (miR-218-5p) was involved in the progression of multiple tumors as a tumor suppressor miRNA. Its specific role on human retinoblastoma (RB) cells remains unknown.
Methods: We constructed the miR-218-5p overexpression and knockdown cells to detect their role on RB cell line WERI-Rb-1, and we analyzed its binding sites on TargetScan. CCK8 and clonogenic assays were performed to detect cell viability. Flow cytometry was used for the detection of cell apoptosis.
Results: Our results showed that the miR-218-5p inhibitor enhanced cell viability and blocked the apoptosis in RB cells. The AKT/mTOR signaling pathway was also inhibited by the miR-218-5p inhibitor. MiR-218-5p mimics lead to diametrically opposite results. Nucleus accumbens-associated 1 (NAC1) encoded by the NACC1 gene is involved in the regulation of many biological functions, including gene transcription, protein degradation of ubiquitin pathway, cell viability, and apoptosis. In this research, dataset analysis suggested that NACC1 might be a downstream target of miR-218-5p. Then, qPCR and Western blot analysis proved that miR-218-5p inhibited the expression of NACC1 in RB cells. NACC1 could promote cell viability and inhibit the apoptosis by activating the AKT/mTOR signaling pathway. MiR-218-5p mimics blocked the enhancement of cell growth induced by NACC1 overexpression as well as the activation of the AKT/mTOR signaling pathway in RB cells.
Discussion: MiR-218-5p inhibited cell growth by targeting NACC1 and suppressing the AKT/mTOR signaling pathway. MiR-218-5p/NACC1/AKT/mTOR might be a new target axis for the clinical treatment strategy.

Keywords: retinoblastoma, miR-218-5p, NACC1, apoptosis, signaling pathway

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]