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环状RNA_0102543通过miR-942-5p/SGTB轴抑制肝细胞癌进展。

Circ_0102543 suppresses hepatocellular carcinoma progression through the miR-942-5p/SGTB axis.

作者信息

Yang Shiming, Wang Dianye, Zhang Rui

机构信息

Department of General Surgery Shanxi Provincial People's Hospital Taiyuan China.

Department of Cardiovascular Affiliated Hospital of Shanxi University of Traditional Chinese Medicine Taiyuan China.

出版信息

Ann Gastroenterol Surg. 2023 Mar 4;7(4):666-677. doi: 10.1002/ags3.12665. eCollection 2023 Jul.

Abstract

INTRODUCTION

Hepatocellular carcinoma (HCC) is one of the most serious cancers. Circular RNA (circRNA) has been reported to regulate the progression of HCC. Herein, the role of circ_0102543 in HCC tumorigenesis was investigated.

MATERIALS

The expression levels of circ_0102543, microRNA-942-5p (miR-942-5p), and small glutamine rich tetratricopeptide repeat co-chaperone beta (SGTB) were detected by quantitative real-time PCR (qRT-PCR). 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) assay, thymidine analog 5-ethynyl-2'-deoxyuridine (EDU) assay, transwell assay, and flow cytometry were conducted to explore the function of circ_0102543 in HCC cells and the regulatory mechanism among circ_0102543, miR-942-5p and SGTB in HCC cells. Western blot examined the related protein levels.

RESULTS

The expression of circ_0102543 and SGTB was decreased in HCC tissues, while the expression of miR-942-5p was increased. Circ_0102543 acted as a sponge for miR-942-5p, and SGTB was the target of miR-942-5p. Circ_0102543 up-regulation hindered tumor growth in vivo. In vitro experiments showed that overexpression of circ_0102543 significantly repressed the malignant behaviors of HCC cells, while co-transfection of miR-942-5p partially attenuated these effects mediated by circ_0102543. In addition, SGTB knockdown increased the proliferation, migration, and invasion of HCC cells inhibited by miR-942-5p inhibitor. Mechanically, circ_0102543 regulated SGTB expression in HCC cells by sponging miR-942-5p.

CONCLUSION

Overexpression of circ_0102543 suppressed proliferation, migration, and invasion of HCC cells by regulating the miR-942-5p/SGTB axis, suggesting that circ_0102543/miR-942-5p/SGTB axis may be a potential therapeutic target for HCC.

摘要

引言

肝细胞癌(HCC)是最严重的癌症之一。据报道,环状RNA(circRNA)可调节HCC的进展。在此,研究了circ_0102543在HCC肿瘤发生中的作用。

材料

通过定量实时PCR(qRT-PCR)检测circ_0102543、微小RNA-942-5p(miR-942-5p)和富含谷氨酰胺的小四肽重复共伴侣β(SGTB)的表达水平。进行3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法、胸苷类似物5-乙炔基-2'-脱氧尿苷(EDU)法、Transwell法和流式细胞术,以探讨circ_0102543在HCC细胞中的功能以及circ_0102543、miR-942-5p和SGTB在HCC细胞中的调控机制。蛋白质印迹法检测相关蛋白水平。

结果

HCC组织中circ_0102543和SGTB的表达降低,而miR-942-5p的表达增加。Circ_0102543作为miR-942-5p的海绵,且SGTB是miR-942-5p的靶标。Circ_0102543上调可抑制体内肿瘤生长。体外实验表明,circ_0102543的过表达显著抑制HCC细胞的恶性行为,而miR-942-5p的共转染部分减弱了circ_0102543介导的这些作用。此外,SGTB敲低增加了受miR-942-5p抑制剂抑制的HCC细胞的增殖、迁移和侵袭。机制上,circ_0102543通过海绵吸附miR-942-5p来调节HCC细胞中SGTB的表达。

结论

circ_0102543的过表达通过调节miR-942-5p/SGTB轴抑制HCC细胞的增殖、迁移和侵袭,提示circ_0102543/miR-942-5p/SGTB轴可能是HCC的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3333/10319616/920e81c053a7/AGS3-7-666-g005.jpg

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