MALAT1 overexpression promotes the growth of colon cancer by repressing β-catenin degradation.

Abstract Colon cancer is one of the most common types of cancer and more than 80% of colon cancer cases are associated with Wnt-β-catenin signaling activation. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a multi-functional long non-coding RNA that is overexpressed in many types of cancers, including colon cancer. In this study, MALAT1 and β-catenin were found to be overexpressed in tumor samples from 62 patients with colon cancer. A positive correlation was identified between MALAT1 levels and β-catenin protein levels in tumors. MALAT1 was found to upregulate β-catenin protein levels in HCT116 and LOVO cells without changing the mRNA expression levels. β-catenin degradation was confirmed to be upregulated in MALAT1-knockdown cells and inhibited in cells overexpressing MALAT1 overexpressing. MALAT1 was then identified as a negative regulator of GSK-3β; it did so via promotion of H3K27 trimethylation of the promoter region. In conclusion, MALAT1 is an oncogene in colon cancer, which inhibits β-catenin degradation by upregulating H3K27 trimethylation and repressing GSK-3β expression.