LncCCAT1 interaction protein PKM2 upregulates SREBP2 phosphorylation to promote osteosarcoma tumorigenesis by enhancing the Warburg effect and lipogenesis
LncCCAT1 interaction protein PKM2 upregulates SREBP2 phosphorylation to promote osteosarcoma tumorigenesis by enhancing the Warburg effect and lipogenesis
复制标题
LncCCAT1相互作用蛋白PKM2上调SREBP2磷酸化通过增强Warburg效应和脂肪生成促进骨肉瘤肿瘤发生
DOI：
10.3892/ijo.2022.5334
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发表时间：
2022-04-01
影响因子：
5.2
通讯作者：
Shao, Zengwu
中科院分区：
文献类型：
--
作者：
Pu, Feifei;Liu, Jianxiang;Shao, Zengwu
丙酮酸激酶 M2 (PKM2) 在葡萄糖消耗和乳酸生成（癌症代谢的显着特征）中发挥着重要作用。 PKM2 与骨肉瘤 (OS) 的关联已有报道，但其在 OS 中的作用尚未阐明。为了研究这一点，我们获得了 HeLa 细胞中 PKM2 结合的 RNA，HeLa 细胞是一种广泛用于分子功能和机制研究的癌细胞。峰识别分析显示 PKM2 与长非编码 RNA (lncRNA) 结合，这与癌症的发病机制和发展相关。对人 OS 细胞系中 PKM2-lncRNA 相互作用的验证表明，lncRNA 结肠癌相关转录物 1 (lncCCAT1) 与 PKM2 相互作用，从而上调甾醇调节元件结合蛋白 2 (SREBP2) 的磷酸化。这些因素促进了 Warburg 效应、脂肪生成和 OS 细胞生长。通过与 lncCCAT1 结合，PKM2 似乎成为操作系统中的关键调节因子。这进一步扩展了 PKM2 在肿瘤发生中的生物学功能，使其成为 OS 的新型潜在治疗方法。
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.