Long noncoding RNA LHFPL3-AS2 suppresses metastasis of non-small cell lung cancer by interacting with SFPQ to regulate TXNIP expression

Abstract

Lung cancer is the most common cancer and the leading cause of cancer deaths worldwide. In addition to coding genes, the contribution of long noncoding RNA (lncRNA) to non-small cell lung cancer (NSCLC) remains unclear. Here, we explored lncRNA expression profiles by Affymetrix Gene Chip Human Transcriptome Array 2.0 in 37 paired samples of tumorous NSCLC tissues and adjacent nontumorous tissues. We showed that LHFPL3-AS2 is a novel lncRNA, significantly decreased in NSCLC tissues. LHFPL3-AS2 was further validated in an additional 93 paired samples of NSCLC. Low levels of LHFPL3-AS2 expression were highly correlated with poor overall survival, TNM stage, and metastasis of NSCLC patients. Enhanced expression of LHFPL3-AS2 inhibited NSCLC invasion and metastasis in vitro and in vivo. Moreover, downregulation of LHFPL3-AS2 reduced its specific interaction with SFPQ, resulting in more SFPQ binding to the promoter of TXNIP and causing the transcriptional repression of TXNIP, thus finally promoting the migration and invasion of NSCLC cells. Furthermore, LHFPL3-AS2 was shown to be regulated by EGR1 under hypoxia.

Keywords: Long noncoding RNA; Metastasis; Non-small cell lung cancer; Thioredoxin interacting protein; Tumor suppressor gene.