Transcriptomic and functional studies reveal miR-431-5p as a tumor suppressor in a pancreatic ductal adenocarcinoma cell line. BxPC-3 mRNA-Seq

The lactate receptor HCAR1 (hydroxycarboxylic acid receptor 1) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), where it regulates lactate transport between the cancer cells. In the present study, we investigated miRNA-mediated regulation of HCAR1 in the PDAC cell line BxPC-3. By searching for predicted miRNA candidates in silico, we identified miR-431-5p as a possible regulator of HCAR1. miR-431-5p overexpression resulted in numerous differentially expressed genes (DEGs), including HCAR1, as identified by mRNA sequencing (mRNA-Seq). A significant proportion of these DEGs was enriched in cancer-related processes and signaling pathways. Functionally, miR-431-5p overexpression inhibited cell proliferation, disrupted cell cycle progression, and induced apoptosis. Small interfering RNA (siRNA)-mediated knockdown of HCAR1 did not affect cell viability. Among the most significantly repressed DEGs was ATP6V0E1, encoding the integral subunit e of vacuolar ATPase (V-ATPase), an enzyme that is important for cancer cell survival. Knockdown of ATP6V0E1 mimicked the effect of miR-431-5p overexpression on cell viability to a large degree. Our findings indicate that miR-431-5p acts as a tumor suppressor in BxPC-3 cells.