LncRNA DICER1‐AS1 promotes colorectal cancer progression by activating the MAPK/ERK signaling pathway through sponging miR‐650

Abstract

AbstractBackgroundColorectal cancer (CRC) is a disease with high morbidity and mortality rates globally. Long noncoding RNAs (lncRNAs) play a fundamental role in tumor progression, and increasing attention has been paid to their role in CRC. This study aimed to determine the function of lncRNA DICER1 antisense RNA 1 (DICER1‐AS1) in CRC and confirm its potential regulatory mechanisms in CRC.MethodsThe publicly available dataset was used to assess DICER1‐AS1 function and expression in CRC. RT–qPCR or western blot assays were performed to verify DICER1‐AS1, miR‐650, and mitogen‐activated protein kinase 1 (MAPK1) expression in CRC cells or tissues. To determine the function of DICER1‐AS1, we performed CCK‐8, colony formation, transwell, cell cycle, and in vivo animal assays. Using RNA sequence analysis, luciferase reporter assays, and bioinformatics analysis, the connection between DICER1‐AS1, MAPK1, and miR‐650 was investigated.ResultsDICER1‐AS1 was significantly upregulated in CRC tissue compared to normal colon tissue. High DICER1‐AS1 expression suggested a poor prognosis in CRC patients. Functionally, upregulation of DICER1‐AS1 effectively promoted CRC proliferation, migration, and invasion ex vivo and tumor progression in vivo. Mechanistically, DICER1‐AS1 functions as a competitive endogenous RNA (ceRNA) that sponges miR‐650 to upregulate MAPK1, promotes ERK1/2 phosphorylation, and sequentially activates the MAPK/ERK signaling pathway.ConclusionOur investigations found that upregulation of DICER1‐AS1 activates the MAPK/ERK signaling pathway by sponging miR‐650 to promote CRC progression, revealing a possible clinically significant biomarker and therapeutic target.