Methylation-mediated LncRNA CRAT40 promotes colorectal cancer progression by recruiting YBX1 to initiate RelA transcription

作者：Q. Richard Lu, Xiu‐He Lv, Jin Wang, Bihan Xia, Hailin Yan, Zhu Wang, Jinlin Yang · 发表于：International Journal of Biological Sciences · 年份：2025 · DOI：10.7150/ijbs.105629 · 被引用次数：2 · 研究领域：Cancer-related molecular mechanisms research、RNA modifications and cancer、RNA Research and Splicing

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Long noncoding RNAs (lncRNAs) have emerged as crucial regulators in the initiation and progression of various malignancies, including CRC. In this study, we found that lnc-CRAT40 was upregulated in CRC and associated with poor prognosis following CRC resection. Functional assays revealed that elevated lnc-CRAT40 expression promotes tumor cell proliferation and metastasis both in vitro and in vivo. The modification of N6-methyladenosine, driven by METTL3, was essential for the stability of lnc-CRAT40, which may partially contribute to the upregulation of lnc-CRAT40. Mechanistically, lnc-CRAT40 directly interacted with Y-box binding protein 1 (YBX1) and recruits it to the RelA promoter, thereby activating NF-κB signaling, which in turn drives CRC proliferation and metastatic potential. These findings provide novel insights into the molecular mechanisms underlying CRC progression and highlight lnc-CRAT40 as a potential prognostic biomarker and therapeutic target.