N6-Methyladenosine Promotes the Transcription of c-Src Kinase via IRF1 to Facilitate the Proliferation of Liver Cancer.

IF 2 4区医学 Q3 ONCOLOGY

Oncology Research Pub Date : 2025-06-26 eCollection Date: 2025-01-01 DOI:10.32604/or.2025.062747

Yanxi Peng, Honggen Yuan, Zhanjie Jiang, Xiaoqing Ou, Qian Zhang, Kexin Yi, Yanbin Meng, Qun Xie

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引用次数: 0

Abstract

Background: Expression of mRNA is widely regulated by N6-methyladenosine (m⁶A). An increasing number of studies have shown that m⁶A methylation, facilitated by methyltransferase 3 (METTL3), is crucial in the progression of tumors. Previous reports have indicated the involvement of both METTL3 and c-Src kinase in the evolution of liver cancer. However, the potential connection between c-Src and the METTL3-mediated mechanism in liver cancer progression remains elusive.

Methods: The correlation expression between c-Src and METTL3 between liver cancer patients and the control group was analyzed using the TCGA database, and was further demonstrated by Western blot and RT-qPCR. The functional roles of c-Src in METTL3-regulated liver cancer progression were investigated by cell proliferation assays and colony formation assays. The regulatory mechanism of METTL3 in c-Src expression was accessed by RNA-immunoprecipitation (RIP)-qPCR.

Results: We demonstrated that c-Src kinase promoted liver cancer development, and the expression of SRC (encodes c-Src kinase) was positively correlated with METTL3 in liver cancer cases. We showed that SRC mRNA could be m⁶A-modified, and METTL3 regulated the transcription of SRC mRNA through interferon regulatory factor 1 (IRF1). We revealed that IRF1, the expression of which was positively regulated by METTL3, was a novel transcription factor of c-Src. Lastly, The pro-proliferative effect of METTL3 on hepatocellular carcinoma was mechanistically linked to IRF1/c-Src axis activation, as evidenced by our experimental data.

Conclusion: Results suggested that the METTL3/IRF1/c-Src axis played potential oncogenic roles in liver cancer development and the axis may be a promising therapeutic target in the disease.

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n6 -甲基腺苷通过IRF1促进c-Src激酶转录促进肝癌增殖

背景：mRNA的表达受n6 -甲基腺苷（m6A）的广泛调控。越来越多的研究表明，甲基转移酶3 （METTL3）促进的m6A甲基化在肿瘤的进展中起着至关重要的作用。先前的报道表明METTL3和c-Src激酶都参与了肝癌的发展。然而，c-Src与mettl3介导的肝癌进展机制之间的潜在联系仍然难以捉摸。方法：采用TCGA数据库分析肝癌患者与对照组c-Src与METTL3的相关表达，并采用Western blot和RT-qPCR进一步验证。通过细胞增殖实验和集落形成实验研究了c-Src在mettl3调控的肝癌进展中的功能作用。采用rna免疫沉淀(RIP)-qPCR方法探讨METTL3对c-Src表达的调控机制。结果：我们发现c-Src激酶促进肝癌的发展，肝癌患者中SRC（编码c-Src激酶）的表达与METTL3呈正相关。我们发现SRC mRNA可以被m6a修饰，并且METTL3通过干扰素调节因子1 （IRF1）调节SRC mRNA的转录。我们发现IRF1是c-Src的一种新的转录因子，其表达受METTL3的正调控。最后，我们的实验数据证明，METTL3对肝细胞癌的促增殖作用与IRF1/c-Src轴激活有关。结论：结果提示METTL3/IRF1/c-Src轴在肝癌的发生发展中具有潜在的致癌作用，该轴可能是该疾病有希望的治疗靶点。

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

Oncology Research 医学-肿瘤学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.