Circular RNA circVAMP3 promotes aerobic glycolysis and proliferation by regulating LDHA in renal cell carcinoma.
Circular RNA circVAMP3 promotes aerobic glycolysis and proliferation by regulating LDHA in renal cell carcinoma.
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环状RNA circVAMP3通过调节肾细胞癌中的LDHA促进有氧糖酵解和增殖
DOI：
10.1038/s41419-022-04863-0
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发表时间：
2022-05-07
影响因子：
9
通讯作者：
Pang, Jun
中科院分区：
文献类型：
--
作者：
Li, Jun;Zhang, Qian;Guan, Yupeng;Liao, Dingzhun;Jiang, Donggen;Xiong, Haiyun;Zhan, Hengji;Pang, Jun
在癌细胞中可以看到代谢功能障碍，其中糖酵解的增加为生长提供能量。环状 RNA (circRNA) 被认为有助于葡萄糖代谢和糖酵解的转变。通过筛选，我们发现circVAMP3对于肾细胞癌（RCC）的糖酵解和增殖活性都是必需的。此外，RCC 患者中 circVAMP3 表达升高，与 TNM 分期相对应。从机制上讲，观察到 circVAMP3 直接与乳酸脱氢酶 A (LDHA) 相互作用并调节其活性。 circVAMP3-LDHA 相互作用促进了上游激酶成纤维细胞生长因子受体 1 型 (FGFR1) 催化的 LDHA 酪氨酸 10 (Y10) 磷酸化。因此，本研究揭示了circVAMP3通过调节糖酵解酶的酶活性促进糖酵解和增殖的新分子机制，表明circVAMP3可能代表RCC生物标志物和治疗靶点。
Metabolic dysfunction is seen in cancer cells where increased glycolysis provides energy for growth. Circular RNAs (circRNAs) are thought to assist in glucose metabolism and the switch to glycolysis. Through screening, we found that circVAMP3 was necessary for both glycolytic and proliferative activities in renal cell carcinoma (RCC). Furthermore, circVAMP3 expression was elevated in RCC patients in correspondence with TNM stage. Mechanistically, circVAMP3 was observed to interact directly with lactate dehydrogenase A (LDHA) and modulate its activity. The circVAMP3–LDHA interaction facilitated LDHA phosphorylation at tyrosine 10 (Y10) catalyzed by the upstream kinase fibroblast growth factor receptor type 1 (FGFR1). Therefore, this study reveals a novel molecular mechanism by which circVAMP3 promotes glycolysis and proliferation through regulating the enzymatic activity of glycolytic enzyme, suggesting that circVAMP3 may represent an RCC biomarker and treatment target.
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DOI：
10.1158/1078-0432.ccr-13-2407
发表时间：
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期刊：
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