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Hsa_circ_0020095 Promotes Oncogenesis and Cisplatin Resistance in Colon Cancer by Sponging miR-487a-3p and Modulating SOX9
Frontiers in Cell and Developmental Biology ( IF 5.5 ) Pub Date : 2020-12-07 , DOI: 10.3389/fcell.2020.604869
Yanlai Sun 1 , Zhen Cao 1, 2 , Junqi Shan 1 , Yang Gao 1 , Xin Liu 1 , Dejian Ma 2 , Zengjun Li 1
Affiliation  

Objectives

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.

Methods

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 in vivo tumor growth assay was applied to further evaluate the effects of circ_0020095 knockdown on CC progression.

Results

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 in vitro and in vivo or by ectopic expression of miR-487a-3p in vitro. 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.

Conclusion

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.



中文翻译:

Hsa_circ_0020095 通过海绵化 miR-487a-3p 和调节 SOX9 促进结肠癌的肿瘤发生和顺铂耐药

Objectives

结肠癌 (CC) 目前是全球第三大最常见的人类癌症,发病率不断增加,预后不良。最近,据报道环状 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。

Methods

测定CC组织和细胞中相关circRNA、microRNA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,采用荧光素酶报告基因实验来验证 miR-487a-3p 与 circ_002009695 或 SOX9 之间的相互作用。此外,体内应用肿瘤生长试验进一步评估 circ_0020095 敲低对 CC 进展的影响。

Results

我们证明了 circ_0020095 在 CC 组织和细胞中高度表达。沉默 circ_0020095 抑制 CC 的增殖、迁移、侵袭和顺铂耐药性体外体内或通过 miR-487a-3p 的异位表达体外. 从机制上讲,circ_0020095 可以直接与 miR-487a-3p 结合,随后充当 miR-487a-3p 海绵,通过靶向 SOX9 的 3'-UTR 来调节活性。有趣的是,circ_0020095 的过表达显着逆转了 miR-487a-3p 模拟物对 CC 细胞的抑制作用。

Conclusion

Circ_0020095 作为癌基因通过 miR-487a-3p/SOX9 轴加速 CC 细胞增殖、侵袭、迁移和顺铂耐药,这可能是 CC 治疗的一个有希望的靶点。

更新日期:2021-01-16
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