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lncRNA MALAT1 potentiates the progression of tongue squamous cell carcinoma through regulating miR-140-5p-PAK1 pathway

Authors Zhu M, Zhang C, Chen D, Chen S, Zheng H

Received 24 October 2018

Accepted for publication 20 January 2019

Published 19 February 2019 Volume 2019:12 Pages 1365—1377

DOI https://doi.org/10.2147/OTT.S192069

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr XuYu Yang


Minhui Zhu,* Caiyun Zhang,* Donghui Chen, Shicai Chen, Hongliang Zheng

Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China

*These authors contributed equally to this work

Background: Tongue squamous cell carcinoma (TSCC) is the second most common malignancy in oral carcinoma. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was regarded as an oncogenic factor in various carcinomas. However, its underlying molecular mechanisms in the development and progression of TSCC have not been well featured till now.
Methods: The expressions of MALAT1, miR-140-5p and p21 (RAC1)-activated kinase 1 (PAK1) mRNA were measured by RT-qPCR assay. The protein level of PAK1 was determined by western blot analysis. Cell viability was detected by Cell Counting Kit-8 assay. Transwell chamber was used to detect cell migratory and invasive capability. Luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and biotin pull-down assay were applied to evaluate the relationship between MALAT1, miR-140-5p and PAK1. Xenograft experiments were performed to assess the effect and mechanism of MALAT1 in TSCC tumor growth.
Results: The expression of MALAT1 and p21 (RAC1)-activated kinase 1 (PAK1) was upregulated and microRNA-140-5p (miR-140-5p) expression was downregulated in TSCC tissues and cells. MALAT1 knockdown induced miR-140-5p expression by direct interaction. Moreover, MALAT1 knockdown inhibited proliferation, migration, and invasion by upregulating miR-140-5p expression in TSCC cells. Additionally, PAK1 was identified as a direct target of miR-140-5p. Also, MALAT1 knockdown inhibited PAK1 expression by upregulating miR-140-5p in TSCC cells. Furthermore, miR-140-5p overexpression curbed the proliferation, migration, and invasion of TSCC cells by targeting PAK1. Finally, MALAT1 knockdown inhibited tumor growth by upregulating miR-140-5p and downregulating PAK1 in mouse xenograft models of TSCC.
Conclusion: MALAT1 contributed to TSCC progression via miR-140-5p-PAK1 regulatory axis, highlighting a potential target for TSCC management.

Keywords: tongue squamous cell carcinoma, lncRNA, MALAT1, miRNA-140-5p, PAK1


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