A‐to‐I RNA Edited miR‐605‐3p Has a Heightened Anti‐Tumor Effect in Colorectal Cancer Through Modulating Immune Infiltration Mediated by CDK6

ABSTRACT Background Adenosine‐to‐inosine (A‐to‐I) RNA editing represents a prevalent post‐transcriptional modification with profound implications for human diseases, particularly cancer. In colorectal cancer (CRC), the specific roles of A‐to‐I editing events remain inadequately understood. This study sought to elucidate the role and underlying mechanism of edited miR‐605‐3p in CRC. Methods The expression levels of miRNA and gene were assessed using RT‐qPCR, Western blotting, and immunohistochemistry. Tumor cell metastasis and proliferation were evaluated through Transwell and CCK‐8 assays, while flow cytometry was utilized to examine tumor cell apoptosis and CD8+ T cell populations. The relationship between gene and miRNA was confirmed via a dual‐luciferase reporter assay. Results In CRC tissues, the A‐to‐I RNA editing level of miR‐605‐3p was found to be elevated, which correlated with favorable clinical outcomes and prognosis in CRC patients. The ADAR2 enzyme is responsible for the overediting of miR‐605‐3p in CRC. Functionally, the wt‐miR‐605‐3p inhibited cell viability and metastasis of CRC, and its anti‐tumor efficacy of miR‐605‐3p was enhanced by A‐to‐I RNA editing. Mechanically, the edited‐miR‐605‐3p directly targets CDK6, in contrast to the wt‐miR‐605‐3p. Overexpression of CDK6 was observed to promote CRC cell proliferation and metastasis by impeding CD8+ T cell immune infiltration. MiR‐605‐3p overediting inhibited CRC tumor growth in vivo by downregulating CDK6. Conclusion The A‐to‐I RNA edited miR‐605‐3p demonstrates a more potent anti‐tumor effect in CRC by modulating CD8+ T cell immune infiltration mediated by CDK6. This study unveils edited miR‐605‐3p as a potential prognostic biomarker and highlights the ADAR2‐miR‐605‐3p axis as a novel therapeutic target for CRC.