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

Journal article

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.

Authors: Lu, Q; Lv, X; Wang, J; Xia, B; Yan, H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Ivyspring International Publisher
• Journal: International Journal of Biological Sciences
• Volume: 21
• Issue: 11
• Pages: 4834-4850
• Publication date: 2025-07-25
• Acceptance date: 2025-07-02
• DOI: 10.7150/ijbs.105629
• EISSN: 1449-2288
• ISSN: 1449-2288
• Pmid: 40860198
• Language: English
• Keywords: RNA, Long Noncoding; Animals; Mice, Inbred BALB C; Y-Box-Binding Protein 1; Mettl3; Gene Expression Regulation, Neoplastic; Methyltransferases; Cell Line, Tumor; Long Non-coding Rna; Disease Progression; Male; Colorectal Neoplasms; Cell Proliferation; Colorectal Cancer; Humans; Ybx1; Mice, Nude; Female; Mice; Transcription Factor RelA