State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, China.
Department of Orthopedics, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.
Cancer Sci. 2023 Jun;114(6):2345-2359. doi: 10.1111/cas.15779. Epub 2023 Mar 21.
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.
骨肉瘤（OS）是最常见的骨原发性恶性肿瘤。最近的研究表明，微小 RNA（miR）-324-3p 的抑制作用可能会影响许多癌症的发展。然而，其在 OS 进展中的生物学作用和潜在机制仍未被探索。在本研究中，miR-324-3p 在 OS 细胞系和组织中的表达明显降低。功能上，miR-324-3p 的过表达抑制了 OS 的进展，并参与了瓦博格效应。在机制上，miR-324-3p 通过靶向其 3'-UTR 负调控磷酸甘油酸变位酶 1（PGAM1）的表达。此外，PGAM1 表达水平升高促进了 OS 的进展和有氧糖酵解，这与 OS 患者的总生存率降低有关。值得注意的是，PGAM1 的过表达部分恢复了 miR-324-3p 的肿瘤抑制功能。总之，miR-324-3p/PGAM1 轴通过调控瓦博格效应在调节 OS 进展中发挥重要作用。我们的研究结果为 miR-324-3p 在葡萄糖代谢中的功能及其在 OS 进展中的作用提供了机制上的见解。靶向 miR-324-3p/PGAM1 轴可能是治疗 OS 的一种有前途的分子策略。
