LncRNA CPS1-IT1 suppresses EMT and metastasis of colorectal cancer by inhibiting hypoxia-induced autophagy through inactivation of HIF-1α

Abstract

Objective: Hypoxia is a common phenomenon in solid tumor microenvironment. Thereby, the aim of this study was to investigate the molecular mechanisms of tumor metastasis and epithelial-mesenchymal transition (EMT) regulated by lncRNA CPS1 intronic transcript 1 (CPS1-IT1) under hypoxia in CRC.

Methods: Expression of lncRNA CPS1-IT1, hypoxia-inducible factor-1 alpha (HIF-1α) and autophagy related protein (LC3) were initially assessed in human CRC tissues and in a series of CRC cell lines. The relationship of CPS1-IT1, HIF-1α and autophagy were analyzed in CRC were performed through in vitro and in vivo functional assays.

Results: Expression of CPS1-IT1 were significantly reduced, while HIF-1α and LC3-II were increased in CRC tissues and cell lines. Then, in vitro assays revealed that CPS1-IT1 suppresses EMT and autophagy by inhibiting the activation of HIF-1α in CRC. An in vivo animal model also demonstrated the tumor suppressor mechanism of CPS1- IT1.

Conclusion: In this study, we found that hypoxia induce autophagy, and inhibition of autophagy could suppress tumor metastasis and EMT in CRC. Additionally, lncRNA CPS1-IT might suppresses metastasis and EMT by inhibiting hypoxia-induced autophagy through inactivation of HIF-1α in CRC.

Keywords: Autophagy; CPS1 intronic transcript 1 (CPS1-IT1); Colorectal carcinoma (CRC); Epithelial-mesenchymal transition (EMT); Hypoxia-inducible factor-1 alpha (HIF-1α).