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Biochimie. 2018 Jan;144:21-27. doi: 10.1016/j.biochi.2017.10.002. Epub 2017 Oct 7.

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

Author information

1
Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Provence, China. Electronic address: weiwei509@yeah.net.
2
Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan Provence, China.

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)

PMID:
29017924
DOI:
10.1016/j.biochi.2017.10.002
[Indexed for MEDLINE]

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