Long noncoding RNA LINC01594 inhibits the CELF6-mediated splicing of oncogenic CD44 variants to promote colorectal cancer metastasis

长链非编码 RNA LINC01594 抑制 CELF6 介导的致癌 CD44 变体剪接,促进结直肠癌转移

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作者:Bowen Liu, Angxi Song, Pengkun Gui, Jin Wang, Yaojie Pan, Chao Li, Shuai Li, Yi Zhang, Tao Jiang, Yixin Xu, Dongsheng Pei, Jun Song

Abstract

Long noncoding RNAs (lncRNAs) play critical roles in tumorigenesis and tumor metastasis. However, the underlying mechanisms of lncRNAs in colorectal cancer (CRC) need further exploration. By using data from The Cancer Genome Atlas (TCGA) and GEO databases, we identified a novel CRC-related lncRNA, LINC01594, that is significantly upregulated in CRC and associated with poor prognosis. In vitro and in vivo, gain- and loss-of-function experiments demonstrated that LINC01594 promotes metastasis in CRC. LINC01594 functions as a DNMT1 scaffold, increasing the level of CELF6 promoter methylation. LINC01594 also competitively binds the transcription factor p53, decreasing CELF6 expression. This inhibited the exon skipping of CD44 V4-V7 induced by CELF6. In summary, this study highlights a novel CRC biomarker and therapeutic target, LINC01594, and the findings suggest that the LINC01594-CELF6-CD44 axis might serve as a biomarker and therapeutic target in CRC.

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