LncCCAT1 interaction protein PKM2 upregulates SREBP2 phosphorylation to promote osteosarcoma tumorigenesis by enhancing the Warburg effect and lipogenesis

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

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作者:Feifei Pu #, Jianxiang Liu #, Doudou Jing #, Fengxia Chen, Xin Huang, Deyao Shi, Wei Wu, Hui Lin, Lei Zhao, Zhenhao Zhang, Xiao Lv, Baichuan Wang, Zhicai Zhang, Zengwu Shao

Abstract

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.

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