miR-338-3p Targets SIRT6 to Inhibit Liver Cancer Malignancy and Paclitaxel Resistance

Abstract

For patients with liver cancer, a widespread and lethal tumor on a global scale, chemotherapy and immunotherapy are often the top choices. Paclitaxel, a widely administered chemotherapy drug, faces the dual issues of poor tumor response rates and the rapid onset of chemoresistance. This study delves into the functions of SIRT6 and miR-338-3p in malignancy and paclitaxel resistance of liver cancer cells. Bioinformatics and qRT-PCR were engaged to predict and examine expression profiles of SIRT6 and miR-338-3p in liver cancer tissues and cell lines. A paclitaxel-resistant cell line (MHCC97-PTX) was established for dissecting cellular responses to drug treatment. CCK-8 and colony formation tests measured cell vitality and proliferation, respectively. Flow cytometry assessed apoptotic cell death, and the paclitaxel IC₅₀ values were derived for each group. We utilized online tools to predict miR-338-3p as an upstream regulator of SIRT6, and a dual-luciferase reporter assay verified their direct interaction. SIRT6 is abundantly expressed in liver cancer tissues and cells. SIRT6 knockdown decreased cell vitality and proliferation while promoting apoptosis and paclitaxel sensitivity. miR-338-3p, an upstream regulator of SIRT6 in liver cancer cells, binds to SIRT6 and downregulates its expression, modulating cell malignancy and drug resistance. The duo of miR-338-3p and SIRT6 can drive the aggressiveness and chemoresistance of liver cancer, emerging as hopeful candidates for biomarkers and therapeutic targets.