环状RNA_0006789通过miR-615-5p/热休克因子1轴促进宫颈癌发展。

circ_0006789 promotes cervical cancer development via the miR-615-5p/HSF1 axis.

作者信息

Zhou Wenyu, Song Weiwei, Lu Meisong

机构信息

Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, No.199 Dazhi Street, Nangang District, Harbin, 150000, Heilongjiang, China.

Department of Gynaecology and Obstetrics, Shenzhen Pingshan District Maternal and Child Health Care Hospital, Shenzhen, 518100, Guangdong, China.

出版信息

Discov Oncol. 2024 May 15;15(1):165. doi: 10.1007/s12672-024-01012-1.

DOI:10.1007/s12672-024-01012-1

PMID:38748048

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11096288/

Abstract

OBJECTIVE

Circular RNAs (circRNAs) are involved in the development of human cancers, including cervical cancer (CC). However, the role and mechanism of circ_0006789 (circSLC25A43) in CC are unclear. The purpose of this study was to investigate the functional role of circ_0006789 in CC.

METHODS

The expression of circ_0006789 in CC tissues and cell lines was examined by RT-qPCR. The characterization of circ_0006789 in CC cells was verified by subcellular localisation, actinomycin D assay, and RNase R assay. After circ_0006789 was knocked down in CC cell lines, the proliferation, apoptosis, migration and invasion of CC cells were assessed by CCK-8 method, flow cytometry, and Transwell assay. RIP assay, FISH assay, dual luciferase reporter gene assay and Western blot were used to investigate the regulatory mechanism between circ_0006789, miR-615-5p and heat shock factor 1 (HSF1).

RESULTS

circ_0006789 was upregulated in CC tissues and cell lines. CC cells were inhibited in their proliferation, migration, and invasion, as well as promoted to apoptosis when circ_0006789 was knocked down. It was found that circ_0006789 targeted miR-615-5p, and miR-615-5p expression was inversely correlated with circ_0006789 expression. Furthermore, HSF1 was a target gene of miR-615-5p. Furthermore, the suppressive effects on HeLa cells mediated by circ_0006789 knockdown were counter-balanced when miR-615-5p was knocked down and HSF1 was overexpressed. Mechanistically, circ_0006789 was found to promote CC development by reducing miR-615-5p and increasing HSF1 expressions.

CONCLUSION

circ_0006789 accelerates CC development via the miR-615-5p/HSF1 axis.

摘要

目的

环状RNA（circRNAs）参与包括宫颈癌（CC）在内的人类癌症的发生发展。然而，circ_0006789（circSLC25A43）在CC中的作用和机制尚不清楚。本研究旨在探讨circ_0006789在CC中的功能作用。

方法

采用RT-qPCR检测circ_0006789在CC组织和细胞系中的表达。通过亚细胞定位、放线菌素D试验和RNase R试验验证circ_0006789在CC细胞中的特征。在CC细胞系中敲低circ_0006789后，采用CCK-8法、流式细胞术和Transwell试验评估CC细胞的增殖、凋亡、迁移和侵袭能力。采用RIP试验、FISH试验、双荧光素酶报告基因试验和蛋白质免疫印迹法研究circ_0006789、miR-615-5p和热休克因子1（HSF1）之间的调控机制。

结果

circ_0006789在CC组织和细胞系中上调。敲低circ_0006789后，CC细胞的增殖、迁移和侵袭受到抑制，同时促进细胞凋亡。研究发现circ_0006789靶向miR-615-5p，且miR-615-5p表达与circ_0006789表达呈负相关。此外，HSF1是miR-615-5p的靶基因。此外，敲低miR-615-5p并过表达HSF1时，可抵消circ_0006789敲低对HeLa细胞的抑制作用。机制上，发现circ_0006789通过降低miR-615-5p表达和增加HSF1表达促进CC发展。