Sun Yanlai, Cao Zhen, Shan Junqi, Gao Yang, Liu Xin, Ma Dejian, Li Zengjun
Department of Gastrointestinal Cancer Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
Front Cell Dev Biol. 2021 Jan 15;8:604869. doi: 10.3389/fcell.2020.604869. eCollection 2020.
Colon cancer (CC) currently ranks as the third most common human cancer worldwide with an increasing incidence and a poor prognosis. Recently, circular RNAs have been reported to regulate the progression of diverse human cancers. However, the role of circRNA hsa_circ_0020095 in CC remains largely unclear.
Expression levels of the related circRNAs, microRNAs and mRNA in CC tissues and cells were determined. The impacts of circ_0020095 or miR-487a-3p on CC cells were examined at the indicated times after transfection. Meanwhile, a luciferase-reporter experiment was employed to validate the interplay between miR-487a-3p and circ_002009695 or SOX9. Moreover, the tumor growth assay was applied to further evaluate the effects of circ_0020095 knockdown on CC progression.
We demonstrated that circ_0020095 was highly expressed in CC tissues and cells. The proliferation, migration, invasion, and cisplatin resistance of CC were suppressed by silencing circ_0020095 and or by ectopic expression of miR-487a-3p . Mechanistically, circ_0020095 could directly bind to miR-487a-3p and subsequently act as a miR-487a-3p sponge to modulate the activity by targeting the 3'-UTR of SOX9. Interestingly, overexpression of circ_0020095 dramatically reversed the suppressive effects of miR-487a-3p mimics on CC cells.
Circ_0020095 functions as an oncogene to accelerate CC cell proliferation, invasion, migration and cisplatin resistance through the miR-487a-3p/SOX9 axis, which could be a promising target for CC treatment.
结肠癌（CC）目前是全球第三大常见人类癌症，发病率不断上升且预后较差。最近，有报道称环状RNA可调节多种人类癌症的进展。然而，circRNA hsa_circ_0020095在CC中的作用仍不清楚。
测定CC组织和细胞中相关环状RNA、微小RNA和mRNA的表达水平。在转染后的指定时间检查circ_0020095或miR-487a-3p对CC细胞的影响。同时，采用荧光素酶报告实验验证miR-487a-3p与circ_002009695或SOX9之间的相互作用。此外，应用肿瘤生长实验进一步评估circ_0020095敲低对CC进展的影响。
我们证明circ_0020095在CC组织和细胞中高表达。沉默circ_0020095和/或异位表达miR-487a-3p可抑制CC的增殖、迁移、侵袭和顺铂耐药性。机制上，circ_0020095可直接与miR-487a-3p结合，随后作为miR-487a-3p的海绵，通过靶向SOX9的3'-UTR来调节其活性。有趣的是，circ_0020095的过表达显著逆转了miR-487a-3p模拟物对CC细胞的抑制作用。
Circ_0020095作为一种癌基因，通过miR-487a-3p/SOX9轴加速CC细胞增殖、侵袭、迁移和顺铂耐药性，这可能是CC治疗的一个有前景的靶点。
