miR-378a, including miR-378a-3p and miR-378a-5p, is encoded in the PPARGC1B gene. It has an active role in regulating multiple metabolic pathways like mitochondrial metabolism and autophagy, and is essential for tumorigenesis, being an independent prognostic biomarker for various malignant tumors. Its aberrant expression impacts processes such as cell proliferation, apoptosis, and metastasis [3,4].

In pancreatic β-cell research, miR378a-3p levels in serum extracellular vesicles were significantly lower in pancreatic β-cell-specific 3-Phosphoinositide-dependent protein kinase 1 (PDK1) knockout mice compared to controls, suggesting it could be a biomarker for pancreatic β-cell mass before diabetes onset [1]. In obesity-related bone deterioration, BMM miR-378a conditional depletion in mice led to obesity-like bone deterioration, indicating its role in enhancing osteogenesis by targeting the Pparα-Abca1 axis in skeletal stem/progenitor cells [2]. In skeletal muscle, miR-378a knockout in mice decreased the number of blood vessels and arterioles in gastrocnemius muscle, showing its role in promoting angiogenesis in skeletal muscle [5].

In conclusion, miR-378a plays crucial roles in metabolism, cancer-related processes, pancreatic β-cell mass regulation, bone deterioration associated with obesity, and angiogenesis in skeletal muscle. Studies using gene knockout mouse models have significantly advanced our understanding of miR-378a's functions in these disease-related areas, providing potential directions for diagnosis and treatment.