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.
*Co-first authors with equal contributions to this work.
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: MiRNA-653, KLF6, Colorectal cancer, CircSETD3, TCGA