MicroRNA‐324‐3p inhibits osteosarcoma progression by suppressing PGAM1‐mediated aerobic glycolysis

Abstract

Osteosarcoma (OS) is the most common primary malignant neoplasm of the bone.Recent studies have indicated that the inhibitory effects of microRNA (miR)-324-3p could affect the development of numerous cancers. However, its biological roles and underlying mechanisms in OS progression remain unexplored. In this study, miR-324-3p expression was markedly reduced in OS cell lines and tissues. Functionally, miR-324-3p overexpression suppressed OS progression and was involved in the Warburg effect. Mechanistically, miR-324-3p negatively regulated phosphoglycerate mutase 1 (PGAM1) expression by targeting its 3′-UTR. Moreover, high expression of PGAM1 promoted OS progression and aerobic glycolysis, which were associated with inferior overall survival in patients with OS. Notably, the tumor suppressor functions of miR-324-3p were partially recovered by PGAM1 overexpression. In summary, the miR-324-3p/PGAM1 axis plays an important role in regulating OS progression by controlling the Warburg effect. Our results provide mechanistic insights into the function of miR-324-3p in glucose metabolism and subsequently on the progression of OS.Targeting the miR-324-3p/PGAM1 axis could be a promising molecular strategy for the treatment of OS.

Pan-Cancer Analysis of PGAM1 and Its Experimental Validation in Uveal Melanoma Progression

“…We found that PGAM1 expression was significantly higher in the majority of solid tumor tissues than in normal tissues. This result is highly consistent with the report of Hitosugi et al [41], indicating that the expression of PGAM1 in tumors is universal and specific. To verify whether the expression of PGAM1 mRNA was consistent with the changes in protein levels, we further analyzed the expression and prognosis of PGAM1 protein in tumors using the HPA database and found that PGAM1 was highly expressed in 9 types of tumors and associated with poor prognosis.…”

“…PGAM1 is a key enzyme involved in glycolysis, and its expression level and functional regulation in a variety of tumors have received extensive attention [41,42]. In this study, we discussed the expression and function of PGAM1 in tumors and its possible regulatory mechanisms from multiple perspectives.…”

“…PGAM1 is an important rate-limiting enzyme of the glycolytic pathway, and its involvement in the regulation of energy metabolism in tumor cells has been widely reported [41]. However, the potential upstream regulatory mechanism of PGAM1 expression itself has rarely been reported.…”

Significance of liquid-liquid phase separation (LLPS)-related genes in breast cancer: a multi-omics analysis

“…Studies have revealed that PGAM1 plays a role in modulating the immune response and influencing immune cell function. It has been found to regulate the metabolic programming of immune cells, particularly T cells and macrophages, thereby impacting their effector functions and immune responses [ 47 ].…”