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LINC00466 Impacts Cell Proliferation, Metastasis and Sensitivity to Temozolomide of Glioma by Sponging miR-137 to Regulate PPP1R14B Expression

Authors Zhao M, Shao Y, Xu J, Zhang B, Li C, Gong J

Received 12 October 2020

Accepted for publication 15 December 2020

Published 19 February 2021 Volume 2021:14 Pages 1147—1159

DOI https://doi.org/10.2147/OTT.S273264

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Mingfei Zhao,1,* Yijie Shao,1,* Jinfang Xu,1 Buyi Zhang,2 Chenguang Li,1 Jie Gong3

1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pathology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Neurointerventional, Zhejiang Hospital of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Jie Gong Tel +86-15168248628
Fax +86571-88098123
Email orchidwave@163.com

Purpose: LINC00466 is a newfound long non-coding RNA (lncRNA) that has been rarely explored in cancers. However, the specific role and molecular mechanism of LINC00466 in glioma remain to be further elucidated.
Methods: Bioinformatic analysis was used to screen differentially expressed genes. Quantitative real-time PCR (qRT-PCR) was used to determine the expression of LINC00466, microRNA-137 (miR-137) and protein phosphatase 1 regulatory subunit 14B (PPP1R14B). Dual-luciferase reporter gene assay and RNA binding protein Immunoprecipitation (RIP) assays were employed to verify the binding relationship among LINC00466, miR-137 and PPP1R14B. The sensitivity of glioma cells to temozolomide (TMZ) was measured by cell counting kit-8 (CCK8) assay. The xenograft nude models were used to test the effects of LINC00466 on glioma tumor growth in vivo.
Results: Highly expressed LINC00466 and PPP1R14B and lowly expressed miR-137 were eventually revealed in glioma tissues. Overexpression of LINC00466 could promote proliferation, metastasis and drug sensitivity to TMZ of glioma cells. LINC00466 could bind to miR-137, and up-regulation of miR-137 could attenuate the enhancing effects caused by LINC00466 overexpression. We took a further step and found that miR-137 could bind to PPP1R14B. Besides, LINC00466 could function as a sponge to miR-137 to regulate PPP1R14B. In addition, overexpression of LINC00466 could promote tumor growth in vivo.
Conclusion: These findings validate LINC00466 could restrain the miR-137 expression to up-regulate PPP1R14B and therefore promote proliferation, metastasis and resistance to TMZ of glioma.

Keywords: LINC00466/miR-137/PPP1R14B, glioma, proliferation and metastasis, temozolomide; TMZ

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