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lncRNA TM4SF1-AS1 Activates the PI3K/AKT Signaling Pathway and Promotes the Migration and Invasion of Lung Cancer Cells

Authors Zhou F, Wang J, Chi X, Zhou X, Wang Z

Received 20 March 2020

Accepted for publication 25 June 2020

Published 7 July 2020 Volume 2020:12 Pages 5527—5536


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 4

Editor who approved publication: Dr Eileen O'Reilly

Fachen Zhou, 1, 2,* Jin Wang, 2,* Xinming Chi, 3 Xin Zhou, 3 Zhou Wang 1

1Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Thoracic Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhou Wang
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, No. 324 Jingwuweiqi Road, Jinan, Shandong Province 250021, People’s Republic of China
Tel +86 53 168777893
Xin Zhou
Department of Histology and Embryology, Dalian Medical University, No. 9 West Part of Lvshun South Road, Dalian, Liaoning Province, People’s Republic of China
Tel +86 41 186110314

Purpose: Metastasis is a crucial cause of the high mortality in patients with lung cancer. Long non-coding RNAs (lncRNAs) are emerging as important players in the development and progression of human cancers. Here, we aimed to identify metastasis-associated lncRNA and to study its roles in the migration and invasion of lung cancer cells.
Materials and Methods: We screened differentially expressed lncRNAs between high- and low-metastatic lung cancer cell lines by using microarray and identified the target lncRNA TM4SF1-AS1. The effect of the TM4SF1-AS1 on the invasion and migration was evaluated through the wound healing experiment and transwell assay. The expression of related genes was assessed by RNA sequence and Western blotting.
Results: TM4SF1-AS1 was highly expressed in high metastatic lung cancer cell line, and it was also significantly up-regulated in lymph node metastatic lung cancer and was associated with lymph node metastasis. Overexpression of TM4SF1-AS1 promoted the migration and invasion of lung cancer cells. Overexpression of TM4SF1-AS1 decreased the expression of E-Cadherin and increased the expression of Vimentin, Snail and Twist, while knockdown of TM4SF1-AS1 exhibited the opposite trend. Furthermore, RNA sequence analysis revealed that some signaling pathways, including PI3K/AKT signaling pathway, were enriched upon TM4SF1-AS1 overexpression. Western blotting further confirmed that the PI3K/AKT signaling pathway was activated by TM4SF1-AS1.
Conclusion: This study illustrates that TM4SF1-AS1 promotes the migration and invasion of lung cancer cells by activating the PI3K/AKT signaling pathway. TM4SF1-AS1 might be a novel target of molecular treatment for lung cancer.

Keywords: lung cancer, long non-coding RNA, TM4SF1-AS1, metastasis, PI3K/AKT signaling pathway

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