Mitochondrial ribosomal protein L3 (MRPL3): An early diagnostic biomarker and potential molecular target in pancreatic cancer.

Pancreatic cancer (PanCa) is projected to become the second major cause of cancer-related mortality by 2030. The current diagnostic and treatment strategies offer only marginal benefits in overall survival. This highlights the need to discover new biomarkers and targets for the treatment of PanCa. Dysregulated mitochondrial ribosome biogenesis occurs in PanCa and can be utilized as a potential biomarker and molecular target for its management. In this study, we established MRPL3 (Mitochondrial Ribosomal Protein L3) as a potential biomarker and its role in expression of ETC (Electron Transport Chain) components. We employed an integrated approach combining the in silico and experimental validation. Our findings demonstrate that the expression of MRPL3 is upregulated during PanCa in ductal adenocarcinoma and other single cell populations of pancreas. Amongst various grades, the highest expression of MRPL3 was observed in grade 1 human PanCa tumors. MRPL3 is involved in the growth of PanCa cells and the targeted knock-down of MRPL3 leads to decrease in the expression of ETC components. Moreover, in silico analysis identified that MRPL3 undergoes alternative splicing that gives rise to six coding and four non-coding variants. The MRPL3-001 isoform arising from ENSG00000114686.8 variant was found to be the most abundant in PanCa. Pathway enrichment analysis showed that MRPL3 is positively associated with cell growth and proliferation while negatively associated with cell lineage commitment and differentiation. These results represent MRPL3 as a promising early biomarker and molecular target for PanCa which warrant further investigation for its clinical applications.