Regulation Mechanism of Long Noncoding RNAs in Colon Cancer Development and Progression

Abstract

Colorectal cancer (CRC) is the second most common cause of cancer-related death worldwide, and its high rates of relapse and metastasis are associated with a poor prognosis. Despite extensive research, the underlying regulatory mechanisms of CRC remain unclear. Long noncoding RNAs (lncRNAs) are a major type of noncoding RNAs that have received increasing attention in the past few years, and studies have shown that they play a role in many biological processes in CRC. Here, we summarize recent studies on lncRNAs associated with CRC and the signaling pathways and mechanisms underlying this association. We show that dysregulated lncRNAs may be new prognostic and diagnostic biomarkers or therapeutic targets for clinical application. This review contributes not only to our understanding of CRC, but also suggests novel signaling pathways associated with lncRNAs that can be targeted to block or eradicate CRC.

Keywords: Colorectal cancer; lncRNA; signaling pathway.

Fig. 1. The diverse regulatory mechanisms of lncRNAs on the Wnt signaling pathway. CCAL can activate Wnt/β-catenin signaling pathway by down-regulating activator protein 2α (AP-2α), which can attenuate β-catenin/TCF-4 interactions and increase β-catenin. CASC11 can interact with hnRNP-K to induce the degradation of β-catenin and activate the Wnt/β-catenin signaling pathway. MALAT1 can increase the nuclear localization of β-catenin and activate the pathway. SNHG1 can increase TCF-4 and β-catenin expression, leading to the nuclear accumulation of β-catenin and activation of the β-catenin pathway. CRNDE and ZEB1-AS1 can activate the Wnt/β-catenin signaling pathway through sponging miR-181a-5p. LincRNA-p21 and CTD903 can reduce the levels of β-catenin in CRC cells. H19 competitively binds to miR-200a and indirectly increases β-catenin expression in CRC. CCAT2 overexpression inhibits β-catenin expression in CRC cells. HNF1A-AS1 can up-regulate the expression of β-catenin, cyclinD1, and c-Myc. LncRNA XIST binds to miR-34a, which can rescue the dysregulation of WNT1 and β-catenin. lncRNA, long noncoding RNA; CRC, colorectal cancer.