ArticleMolecular medicine (Cambridge, Mass.)2026
MIR133B-SEPT9 axis suppresses colorectal cancer progression by inhibiting β-catenin-mediated EMT signaling and is associated with poor prognosis.
Article in Molecular medicine (Cambridge, Mass.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMIR133B is a colorectal cancer (CRC)-associated gene, and its mature product, miR-133b, is significantly downregulated in CRC tissues.
methodsWe aimed to elucidate the tumor-suppressive role of miR-133b in CRC. To identify its downstream target genes, we compared the transcriptome of miR-133b-overexpressing cells with bioinformatic predictions and identified 23 potential target genes. We focused on SEPT9, a gene involved in tumor progression. We confirmed that SEPT9 is a direct target of miR-133b and investigated its role in cell proliferation, invasion, and epithelial-mesenchymal transition (EMT). In addition, we evaluated the expression and prognostic relevance of SEPT9 and active β-catenin in 219 patients with CRC.
resultsWe confirmed the direct interaction between miR-133b and SEPT9 using luciferase reporter assay, qRT-PCR, and western blot. SEPT9 expression was significantly upregulated in CRC tissues compared with that in adjacent normal controls. In HCT116 and SW48 CRC cell lines, overexpression of miR-133b or knockdown of SEPT9 significantly reduced SEPT9 protein levels; suppressed proliferation, colony formation, and invasiveness; inhibited KRAS, BRAF, PI3K, pAKT, and pERK expression; and regulated EMT by downregulating N-cadherin, Vimentin, Snail, Twist, and active β-catenin while upregulating E-cadherin. Nuclear SEPT9 expression positively correlated with active β-catenin in human CRC tissues. In multivariate analysis, SEPT9 positivity independently predicted poor OS and RFS, and the combined SEPT9/active β-catenin expression pattern was an independent predictor of OS for both subgroups and of RFS specifically for the co-positive (SEPT9+/active β-catenin+) subgroup.
conclusionThis study suggests that miR-133b suppresses CRC progression by directly targeting SEPT9 and inhibiting β-catenin-mediated EMT, as well as identifies the miR-133b-SEPT9-β-catenin axis as a potential prognostic indicator in patients with CRC.
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