Hypoxia-induced miR-653 enhances colorectal cancer progression by targeting circSETD3/KLF6 axis

Qian Chen; Qingchun Deng; Yinglian Pan; Xiangwu Ding; Jing Liu

doi:10.7150/jca.78865

Hypoxia-induced miR-653 enhances colorectal cancer progression by targeting circSETD3/KLF6 axis

J Cancer. 2023 Jan 1;14(1):163-173. doi: 10.7150/jca.78865. eCollection 2023.

Authors

Qian Chen¹, Qingchun Deng², Yinglian Pan³, Xiangwu Ding¹, Jing Liu⁴

Affiliations

¹ Department of Gastroenterology, Wuhan Fourth Hospital, Wuhan 430033, China.
² Department of Gynecology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570216, China.
³ Department of Medical Oncology, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, China.
⁴ Department of Neurology, Wuhan Fourth Hospital, Wuhan 430033, China.

Abstract

The present work focused on exploring the role and underlying molecular mechanism of action of the non-coding RNA (miRNA/circRNA) in colorectal cancer (CRC). Here, we found that miR-653 was dramatically upregulated in CRC tissues and cells. CRC Patients with high miR-653 level possessed poor prognosis. miR-653 elevated proliferation, migration, and invasion, meanwhile suppressed apoptosis of CRC cells. Furthermore, circSETD3 directly sponged miR-653 and negatively regulate miR-653 to affect proliferation, migration, invasion, and apoptosis of CRC cells. Moreover, miR-653 served as carcinoma-promoting gene via targeting KLF6, and circSETD3 knockdown significantly reversed the inhibitory effect of KLF6 overexpression on CRC cells. In addition, hypoxia obviously increased expression of miR-653. Knockdown of miR-653 decreased the effects of hypoxia on CRC cell proliferation, migration and invasion. Taken together, these findings indicated that circSETD3/miR-653/KLF6 axis may be an effective therapeutic target for CRC patients.

Keywords: CircSETD3; Colorectal cancer; KLF6; MiRNA-653; TCGA.