Chen Qian, Deng Qingchun, Pan Yinglian, Ding Xiangwu, Liu Jing
Department of Gastroenterology, Wuhan Fourth Hospital, Wuhan 430033, China.
Department of Gynecology, The Second Affiliated Hospital of Hainan Medical University, Haikou 570216, China.
J Cancer. 2023 Jan 1;14(1):163-173. doi: 10.7150/jca.78865. eCollection 2023.
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.
本研究聚焦于探索非编码RNA（miRNA/circRNA）在结直肠癌（CRC）中的作用及潜在分子作用机制。在此，我们发现miR-653在CRC组织和细胞中显著上调。miR-653水平高的CRC患者预后较差。miR-653促进CRC细胞的增殖、迁移和侵袭，同时抑制其凋亡。此外，circSETD3直接吸附miR-653并对其产生负向调节作用，从而影响CRC细胞的增殖、迁移、侵袭及凋亡。而且，miR-653通过靶向KLF6发挥促癌基因的作用，敲低circSETD3可显著逆转KLF6过表达对CRC细胞的抑制作用。此外，缺氧明显增加miR-653的表达。敲低miR-653可降低缺氧对CRC细胞增殖、迁移和侵袭的影响。综上所述，这些发现表明circSETD3/miR-653/KLF6轴可能是CRC患者的一个有效治疗靶点。
