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Background  Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target.    Methods  We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with  LINRIS  (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with  LINRIS  inhibited were tested in vitro and in vivo .Results   LINRIS  was upregulated in CRC tissues from patients with poor overall survival (OS), and  LINRIS  inhibition led to the impaired CRC cell line growth. Moreover, knockdown of  LINRIS  resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N 6 -methyladenosine (m 6 A) ‘reader’.  LINRIS  blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of  LINRIS  attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of  LINRIS  could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of  LINRIS  suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models.    Conclusion   LINRIS  is an independent prognostic biomarker for CRC. The  LINRIS -IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.

LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer