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环状RNA_102272通过减少miR-326对RUNX2的靶向作用促进肝癌顺铂耐药

CircRNA_102272 Promotes Cisplatin-Resistance in Hepatocellular Carcinoma by Decreasing MiR-326 Targeting of RUNX2.

作者信息

Guan Yonghai, Zhang Ying, Hao Lina, Nie Zhenwang

机构信息

Department of Infectious Diseases, The Second Hospital of Dalian Medical University, Dalian 116023, Liaoning, People's Republic of China.

Sixth Department of Liver Diseases, The Sixth People's Hospital of Dalian, Dalian Medical University, Dalian 116031, Liaoning, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Dec 7;12:12527-12534. doi: 10.2147/CMAR.S258230. eCollection 2020.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the leading cause of tumor-associated death in males and females worldwide. HCC is mostly diagnosed at advanced stages and the chemotherapeutic cisplatin is one of the major therapeutic options in the treatment of patients with treating advanced HCC. Despite several reports on HCC multidrug resistance, the underlying regulatory mechanisms are still unclear.

METHODS

RT-PCR was performed to detect circRNA_102272, miR-326 and RUNX2 expression. The CCK8 assay was used to examine cell proliferation and cisplatin IC values. The luciferase reporter assay was performed to verify complementary combinations between circRNA_102272 and miR-326 and between miR-326 and RUNX2.

RESULTS

CircRNA_102272 expression was upregulated in HCC tissues and cells. CircRNA_102272 knockdown suppressed HCC cell proliferation and decreased cisplatin-resistance. In addition, circRNA_102272 facilitated HCC cisplatin-resistance by regulating the miR-326/RUNX2 axis.

CONCLUSION

CircRNA_102272 is significantly increased in HCC tissues and cells and promotes HCC cell proliferation and cisplatin-resistance. More importantly, circRNA acts as a ceRNA to suppress the expression and activity of miR-326, leading to the increase in RUNX2 expression. By elucidating circRNA_102272 role and mechanism of action in HCC, our study provides insights and an opportunity to overcome cisplatin-resistance in HCC.

摘要

背景

肝细胞癌(HCC)是全球男性和女性肿瘤相关死亡的主要原因。HCC大多在晚期被诊断出来,化疗药物顺铂是治疗晚期HCC患者的主要治疗选择之一。尽管有几篇关于HCC多药耐药性的报道,但其潜在的调控机制仍不清楚。

方法

采用逆转录聚合酶链反应(RT-PCR)检测circRNA_102272、miR-326和RUNX2的表达。采用细胞计数试剂盒(CCK8)检测细胞增殖和顺铂半数抑制浓度(IC值)。进行荧光素酶报告基因检测以验证circRNA_102272与miR-326之间以及miR-326与RUNX2之间的互补结合。

结果

circRNA_102272在HCC组织和细胞中表达上调。敲低circRNA_102272可抑制HCC细胞增殖并降低顺铂耐药性。此外,circRNA_102272通过调节miR-326/RUNX2轴促进HCC顺铂耐药性。

结论

circRNA_102272在HCC组织和细胞中显著增加,促进HCC细胞增殖和顺铂耐药性。更重要的是,circRNA作为一种竞争性内源RNA(ceRNA)抑制miR-326的表达和活性,导致RUNX2表达增加。通过阐明circRNA_102272在HCC中的作用和作用机制,我们的研究为克服HCC顺铂耐药性提供了思路和机会。

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