The role of lncRNA LSAT1 in the invasion and metastasis of non-small cell lung cancer under hypoxia

Lei Zhang; Zhi-Yong Wan; Xiang Zhang; Jun Liu; Wei-Yi Huang; Yu-Bing Zhao

doi:10.21037/tcr.2019.12.101

The role of lncRNA LSAT1 in the invasion and metastasis of non-small cell lung cancer under hypoxia

Transl Cancer Res. 2020 Feb;9(2):1125-1132. doi: 10.21037/tcr.2019.12.101.

Authors

Lei Zhang¹, Zhi-Yong Wan¹, Xiang Zhang¹, Jun Liu¹, Wei-Yi Huang¹, Yu-Bing Zhao¹

Affiliation

¹ Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.

Abstract

Background: To investigate the role of lncRNA LSAT1 in the hypoxia-induced invasion and metastasis of non-small cell lung cancer (NSCLC).

Methods: High-throughput microarrays were used to compare the lncRNA expression profile difference between normoxia-induced and hypoxia-induced NSCLC cell lines including A549, NCI-H1650 and NCI-H1299 in order to preliminarily screen key molecules related to hypoxia-induced invasion and metastasis of NSCLC. The different expression of lncRNA LSAT1 was measured in hypoxia-induced NSCLC cells (compared to normoxia-induced NSCLC cells) and 20 pairs of NSCLC tissues (compared to adjacent tissues) with RT-PCR. The expression of lncRNA LSAT1 in NSCLC cells A549 and NCI-H1299 was down-regulated by lentiviral transfection. Transwell migration and invasion assays and tail vein injection metastasis assay were employed for investigating the effect of lncRNA LSAT1 knockdown on the hypoxia-induced invasion and metastasis of NSCLC cells.

Results: RT-PCR showed that lncRNA LSAT1 was significantly increased in hypoxia-induced NSCLC cells A549, NCI-H1650 and NCI-H1299 and compared with adjacent tissues. The expression of lncRNA LSAT1 was also upregulated in NSCLC tissues. Transwell migration and invasion assays demonstrated that hypoxia could enhance the abilities of migration and invasion of NSCLC cells A549 and NCI-H1299. However, these two abilities were significantly inhibited after lncRNA LSAT1 knockdown. In addition, nude mice tail vein injection metastasis assay also verified that lncRNA LSAT1 knockdown inhibited liver metastasis and lung metastasis of NSCLC cell A549 in vivo.

Conclusions: We found a series of hypoxia-related lncRNAs in NSCLC by means of high-throughput screening microarrays. Clinical specimen analysis and functional loss test confirmed that lncRNA LSAT1 is a key lncRNA for hypoxia-induced invasion and metastasis of NSCLC. In addition, STAT3 may be one of the target genes for lncRNA LSAT1 to play a regulatory role.

Keywords: Non-small cell lung cancer (NSCLC); hypoxia; long non-coding RNA-LSAT1 (lncRNA-LSAT1); metastasis.