To determine whether microRNA (miR)-129 regulating colon cancer cell proliferation by targeting the cationic amino acid transporter 1(CAT-1) and thus modulating arginine metabolism.

Expression of CAT-1 and miR-129 was examined in 93 paired colon cancer tissues using real-time fluorogenic quantitative PCR (qPCR) and immunohistochemistry (tissue microarray) from Shanghai East Hospital. Bioinformatics predicted their targeting relationship. In RKO cells, gain-and loss-of-function models for miR-129 were established. Western blotting, enzyme-linked immunosorbent assay (ELISA), and CCK-8 assays were used to assess CAT-1 protein, intracellular arginine, and proliferation.

CAT-1 was upregulated and miR-129 downregulated in tumors. miR-129 was bioinformatically predicted to bind the 3'-UTR of CAT-1. Functionally, cell proliferation was arginine-dependent. Overexpression of miR-129 suppressed CAT-1, decreased intracellular arginine, and inhibited proliferation, while miR-129 knockdown had opposing effects.

miR-129 functions as a tumor suppressor in colon cancer by targeting CAT-1, thereby negatively regulating arginine uptake and cell proliferation. This defines a critical miR-129/CAT-1/arginine metabolic axis.