Oncogenic Function of miR-182-5p Versus Tumor-Suppressive Activities of miR-203, miR-150-5p, and miR-139-5p via Target Gene Regulation in Colon Cancer Metastasis

miR-182-5p 的致癌功能与 miR-203、miR-150-5p 和 miR-139-5p 通过靶基因调控在结肠癌转移中的抑癌活性

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Abstract

BACKGROUND: MicroRNAs (miRNAs) play key roles in colorectal cancer (CRC) progression and metastasis. miR-182-5p acts as an oncogenic metastamiR, frequently upregulated in cancers and promoting cell migration and invasion. In contrast, miR-203, miR-150-5p, and miR-139-5p function as tumor suppressors and are often downregulated in CRC. METHODS: Expression levels of these four miRNAs were quantified in three CRC cell lines using real-time polymerase chain reaction (RT-PCR). Functional assays, including cell viability, migration, and invasion, were conducted after silencing miR-182-5p or overexpressing the tumor-suppressive miRNAs through mimic transfection. RESULTS: The miR-182-5p was significantly overexpressed and positively correlated with metastatic potential, while miR-203, miR-150-5p, and miR-139-5p were downregulated and inversely associated with metastatic traits. Modulation of these miRNAs reduced CRC cell viability, migration, and invasion. Mechanistically, miR-182-5p enhanced metastasis via ANLN and PDE4D regulation, whereas miR-203, miR-150-5p, and miR-139-5p suppressed metastasis through PDE4D, NEGR1, and ATP11A pathways, respectively. CONCLUSIONS: These results highlight the opposing roles of miR-182-5p and the tumor-suppressive miRNAs in CRC metastasis and suggest their potential as biomarkers and therapeutic targets.

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