m6A-modified circASXL1 promotes proliferation and migration of ovarian cancer through the miR-320d/RACGAP1 axis.

IF 3.3 3区医学 Q2 ONCOLOGY Carcinogenesis Pub Date : 2023-12-30 DOI:10.1093/carcin/bgad066

Qi Tian, Qingling Mu, Shuang Liu, Kui Huang, Yi Tang, Pu Zhang, Jing Zhao, Chuqiang Shu

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Abstract

Ovarian cancer (OC) is one of the most common malignant tumors in women. Circular RNAs (circRNAs) can potentially regulate the development of OC. Therefore, this study investigated the role of circASXL1 in OC progression. Cell functions were assessed by MTT, colony formation, wound healing, and transwell assays. RIP and dual luciferase reporter assays confirmed the relationship between miR-320d and circASXL1 or RACGAP1. MeRIP was utilized to detect m6A levels. Xenograft tumor was established for in vivo experiments. CircASXL1 and RACGAP1 levels were increased in OC tissues and cells, whereas miR-320d expression was decreased. Upregulation of circASXL1 was associated with poor prognosis in OC patients. CircASXL1 silencing suppressed OC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, METTL3/IGF2BP1-mediated m6A modification maintained circASXL1 stability and upregulated its expression. CircASXL1 was a ceRNA that sequestrated miR-320d from RACGAP1, leading to increased RACGAP1 expression. CircASXL1 promoted OC cell proliferation, migration and invasion via the miR-320d/RACGAP1 axis. Therefore, m6A-modified circASXL1 acts as an oncogene in OC by targeting miR-320d and activating RACGAP1/PI3K/Akt pathway, which provides novel promising biomarkers for OC diagnosis.

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m6A-修饰的circASXL1通过miR-320d/RACGAP1轴促进卵巢癌症的增殖和迁移。

癌症是女性最常见的恶性肿瘤之一。环状RNA（circRNAs）可以潜在地调节OC的发展。因此，本研究探讨了circASXL1在OC进展中的作用。通过MTT、集落形成、伤口愈合和transwell测定来评估细胞功能。RIP和双荧光素酶报告基因测定证实了miR-320d与circASXL1或RACGAP1之间的关系。利用MeRIP检测m6A水平。异种移植瘤是为体内实验而建立的。OC组织和细胞中CircASXL1和RACGAP1水平升高，而miR-320d表达降低。circASXL1的上调与OC患者的不良预后相关。CircASXL1沉默抑制了OC细胞在体外和体内的增殖、迁移和侵袭。从机制上讲，METTL3/IGF2BP1介导的m6A修饰维持了circASXL1的稳定性并上调了其表达。CircASXL1是一种从RACGAP1中分离miR-320d的ceRNA，导致RACGAP1表达增加。CircASXL1通过miR-320d/RACGAP1轴促进OC细胞增殖、迁移和侵袭。因此，m6A修饰的circASXL1通过靶向miR-320d并激活RACGAP1/PI3K/Akt途径，在OC中发挥致癌基因的作用，为OC诊断提供了新的有前景的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Carcinogenesis 医学-肿瘤学

CiteScore

9.20

自引率

2.10%

发文量

审稿时长

1 months

期刊介绍： Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).