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

Fachen Zhou; Jin Wang; Xinming Chi; Xin Zhou; Zhou Wang

doi:10.2147/CMAR.S254072

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

Cancer Manag Res. 2020 Jul 7:12:5527-5536. doi: 10.2147/CMAR.S254072. eCollection 2020.

Authors

Fachen Zhou^#^{1

2}, Jin Wang^#², Xinming Chi³, Xin Zhou³, Zhou Wang¹

Affiliations

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

^# Contributed equally.

Abstract

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

Grants and funding

This work was supported by Liaoning Provincial Natural Science Foundation (No.20180551083) and Dalian medical scientific Research Foundation (No.1812015).