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人源环状RNA hsa_circ_0072088通过调控miR-1270/TOP2A轴促进非小细胞肺癌进展。

Hsa_circ_0072088 promotes non-small cell lung cancer progression through modulating miR-1270/TOP2A axis.

作者信息

Li Sixuan, Cui Zhigang, Gao Min, Shan Yanan, Ren Yihong, Zhao Yuxin, Wang Di, Meng Tingyu, Liu Hongxu, Yin Zhihua

机构信息

Postdoctoral Research Station, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital & Institute, Shenyang, 110042, China.

Department of Epidemiology, School of Public Health, China Medical University, Shenyang, 110122, Liaoning, China.

出版信息

Cancer Cell Int. 2025 Apr 21;25(1):156. doi: 10.1186/s12935-025-03749-3.

Abstract

According to the data released by the International Agency for Research on Cancer (IARC) in 2020, lung cancer ranks second among newly diagnosed malignant tumors globally. As a special class of non-coding RNA, circRNA has become a new hotspot in the field of biomarker research. With the continuous deepening of molecular-level investigations, the underlying mechanisms of circRNA are being gradually unveiled. The more widely studied mechanism is the competitive endogenous RNA mechanism of circRNA. Studies related to circRNA expression were searched in GEO database and statistically analyzed using the "limma" package and weighted gene co-expression network analysis. The expression of circRNA, microRNA and mRNA in cells and tissues were examined via qRT-PCR. MTS assay was used to measure cell proliferation, Transwell assay was used to measure cell migration, and apoptosis assay was carried out to detect cell apoptosis. Additionally, a dual-luciferase reporter assay was further executed to explore the targeted binding relationships between circRNA-microRNA and microRNA-mRNA. It was discovered that hsa_circRNA_103809 was differentially highly expressed in non-small cell lung cancer cells, whereas miR-1270 was differentially lowly expressed. The knockdown of circ_0072088 inhibited the cell proliferation and migration, while promoting cell apoptosis. The same biological function was found with the overexpression of miR-1270. The rescue experiment further validated that circ_0072088 could regulate the biological function of cells by influencing miR-1270. Finally, the targeted binding relationship was verified by dual luciferase reporting experiment. In conclusion, circ_0072088 is differentially highly expressed in non-small cell lung cancer and can affect the progression of non-small cell lung cancer through the circ_0072088/miR-1270/TOP2A axis.

摘要

根据国际癌症研究机构(IARC)2020年发布的数据,肺癌在全球新诊断的恶性肿瘤中排名第二。作为一类特殊的非编码RNA,环状RNA(circRNA)已成为生物标志物研究领域的一个新热点。随着分子水平研究的不断深入,circRNA的潜在机制正逐渐被揭示。研究较多的机制是circRNA的竞争性内源性RNA机制。在GEO数据库中搜索与circRNA表达相关的研究,并使用“limma”软件包和加权基因共表达网络分析进行统计分析。通过qRT-PCR检测细胞和组织中circRNA、微小RNA(miRNA)和信使RNA(mRNA)的表达。采用MTS法检测细胞增殖,Transwell法检测细胞迁移,并进行凋亡检测以检测细胞凋亡。此外,进一步进行双荧光素酶报告基因检测以探索circRNA-miRNA和miRNA-mRNA之间的靶向结合关系。研究发现,hsa_circRNA_103809在非小细胞肺癌细胞中差异高表达,而miR-1270差异低表达。敲低circ_0072088可抑制细胞增殖和迁移,同时促进细胞凋亡。miR-1270过表达也发现了相同的生物学功能。挽救实验进一步验证了circ_0072088可通过影响miR-1270来调节细胞的生物学功能。最后,通过双荧光素酶报告实验验证了靶向结合关系。综上所述,circ_0072088在非小细胞肺癌中差异高表达,并可通过circ_0072088/miR-1270/TOP2A轴影响非小细胞肺癌的进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4182/12010575/714139b874d5/12935_2025_3749_Fig1_HTML.jpg

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