microRNA 6125 (miR-6125)

microRNA 6125 (miR-6125) is a human microRNA and a member of the miRNA family, small non-coding RNAs that regulate gene expression through binding to complementary sequences in target mRNAs, leading to mRNA destabilization or translational inhibition. miR-6125 is significantly downregulated in colorectal cancer tissues and cell lines, with lower expression linked to increased tumor size and poorer prognosis. Mechanistically, miR-6125 targets the mRNA of YTHDF2, a reader of RNA N6-methyladenosine (m6A) modification, and suppresses its expression. This results in increased stability of m6A-modified GSK3β mRNA, activating GSK3β protein, which in turn inhibits the Wnt/β-catenin signaling pathway, leading to cell cycle arrest and reduced proliferation of cancer cells. miR-6125 is thus regarded as a potential therapeutic target and biomarker for colorectal cancer, and may play additional roles in other biological processes as a gene expression regulator.

Other names

MIR6125hsa-mir-6125mir-6125microRNA mir-6125

miR-6125 binds to the 3′ untranslated region (UTR) of YTH Domain-Containing Family Protein 2 (YTHDF2) mRNA, suppressing its translation and protein levels. Downregulation of YTHDF2 by miR-6125 increases the stability of m6A-modified glycogen synthase kinase 3 beta (GSK3β) mRNA, leading to increased GSK3β protein, inhibition of Wnt/β-catenin/Cyclin D1 pathway-related proteins, and cell cycle arrest (G0-G1 phase), ultimately inhibiting proliferation of colorectal cancer cells.