@Article{or.2025.062747,
AUTHOR = {Yanxi Peng, Honggen Yuan, Zhanjie Jiang, Xiaoqing Ou, Qian Zhang, Kexin Yi, Yanbin Meng, Qun Xie},
TITLE = {N6-Methyladenosine Promotes the Transcription of c-Src Kinase via IRF1 to Facilitate the Proliferation of Liver Cancer},
JOURNAL = {Oncology Research},
VOLUME = {33},
YEAR = {2025},
NUMBER = {7},
PAGES = {1679--1693},
URL = {http://www.techscience.com/or/v33n7/62638},
ISSN = {1555-3906},
ABSTRACT = { <b>Background:</b> Expression of mRNA is widely regulated by N6-methyladenosine (m<sup>6</sup>A). An increasing number of studies have shown that m<sup>6</sup>A 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. <b>Methods:</b> 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. <b>Results:</b> We demonstrated that c-Src kinase promoted liver cancer development, and the expression of <i>SRC</i> (encodes c-Src kinase) was positively correlated with METTL3 in liver cancer cases. We showed that <i>SRC</i> mRNA could be m<sup>6</sup>A-modified, and METTL3 regulated the transcription of <i>SRC</i> 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. <b>Conclusion:</b> 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.},
DOI = {10.32604/or.2025.062747}
}