Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Department of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei 430071, P.R. China.
Int J Oncol. 2022 Apr;60(4). doi: 10.3892/ijo.2022.5334. Epub 2022 Mar 4.
Pyruvate kinase M2 (PKM2) plays an important role in the consumption of glucose and the production of lactic acid, the striking feature of cancer metabolism. The association of PKM2 with osteosarcoma (OS) has been reported but its role in OS has yet to be elucidated. To study this, PKM2‑bound RNAs in HeLa cells, a type of cancer cells widely used in the study of molecular function and mechanism, were obtained. Peak calling analysis revealed that PKM2 binds to long noncoding RNAs (lncRNAs), which are associated with cancer pathogenesis and development. Validation of the PKM2‑lncRNA interaction in the human OS cell line revealed that lncRNA colon cancer associated transcript‑1 (lncCCAT1) interacted with PKM2, which upregulated the phosphorylation of sterol regulatory element‑binding protein 2 (SREBP2). These factors promoted the Warburg effect, lipogenesis, and OS cell growth. PKM2 appears to be a key regulator in OS by binding to lncCCAT1. This further extends the biological functions of PKM2 in tumorigenesis and makes it a novel potential therapeutic for OS.
丙酮酸激酶 M2(PKM2)在葡萄糖消耗和乳酸生成中发挥重要作用,这是癌症代谢的显著特征。已经有报道称 PKM2 与骨肉瘤(OS)有关,但它在 OS 中的作用尚未阐明。为了研究这一点,获得了在 HeLa 细胞(一种常用于研究分子功能和机制的癌细胞)中与 PKM2 结合的 RNA。峰调用分析显示,PKM2 与长非编码 RNA(lncRNA)结合,lncRNA 与癌症的发病机制和发展有关。在人骨肉瘤细胞系中验证 PKM2-lncRNA 相互作用发现,lncRNA 结肠癌相关转录物-1(lncCCAT1)与 PKM2 相互作用,上调固醇调节元件结合蛋白 2(SREBP2)的磷酸化。这些因素促进了沃伯格效应、脂肪生成和 OS 细胞生长。PKM2 通过与 lncCCAT1 结合,似乎成为 OS 的关键调节因子。这进一步扩展了 PKM2 在肿瘤发生中的生物学功能,并使其成为 OS 的一种新的潜在治疗方法。