Acta Biochimica et Biophysica Sinica (May 2023)
lncRNA RMST suppresses the progression of colorectal cancer by competitively binding to miR-27a-3p/RXRα axis and inactivating Wnt signaling pathway
Abstract
Colorectal cancer (CRC) ranks the 3rd in cancer types globally. Long noncoding RNAs (lncRNAs) are related to the initiation and progression of CRC. The current study plans to reveal the action of rhabdomyosarcoma 2-associated transcript (RMST) in CRC. The results show that RMST is downregulated in CRC specimens and cell lines relative to normal specimens and a fetal normal colon cell line (FHC), respectively. Elevation of RMST represses cell proliferation and colony formation and induces cell apoptosis in CRC cells. Bioinformatic analysis reveals a binding site in RMST for miR-27a-3p. The direct association between RMST and miR-27a-3p is confirmed by dual luciferase reporter assay, RNA pull-down assay, and real time-quantitative polymerase chain reaction (RT-qPCR). miR-27a-3p is upregulated in CRC tumor specimens relative to normal specimens, and there is a negative correlation between RMST and miR-27a-3p in CRC tumor specimens. In addition, the effects of RMST overexpression are weakened by the elevation of miR-27a-3p. RMST and retinoid X receptor (RXRα) share the same complementary site with miR-27a-3p. The direct association between RXRα and miR-27a-3p is confirmed by RNA pull-down assay, RT-qPCR and western blot analysis. Overexpression of RMST induces RXRα expression and inactivates the Wnt signaling pathway by decreasing β-catenin levels in CRC cells. Collectively, our findings reveal a pivotal role of RMST in regulating miR-27a-3p/RXRα axis and counteracting Wnt signaling pathway during the progression of CRC.
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