Department of Urology, Anhui Provincial Hospital, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science & Technology of China (USTC), Hefei, Anhui 230001, China.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
Oxid Med Cell Longev. 2022 May 2;2022:8693259. doi: 10.1155/2022/8693259. eCollection 2022.
It is known that the long noncoding RNAs (lncRNA) MALAT1 is associated with tumorigenesis and progression in various cancers; however, its functions and mechanisms in prostate cancer (PCa) initiation and progression are still unknown. In the present study, our findings revealed that MALAT1 plays a critical part in regulating PCa proliferation and glucose metabolism. Knockdown of MALAT1 affects the protein and mRNA levels of MYBL2. In addition, MALAT1 enhances the phosphorylation level of mTOR pathway by upregulating MYBL2. Knockdown of MALAT1 or MYBL2 in PCa cell lines significantly inhibits their proliferation capacity. Silencing MALAT1/MYBL2/mTOR axis in PCa cell lines affects their glycolysis and lactate levels, and we verified these findings in mice. Furthermore, we explored the underlying tumorigenesis functions of MYBL2 in PCa and found that high expression of MYBL2 was positively associated with TNM stage, Gleason score, PSA level, and poor survival rate in PCa patients. Taken together, our research suggests that MALAT1 controls cancer glucose metabolism and progression by upregulating MYBL2-mTOR axis.
已知长链非编码 RNA（lncRNA）MALAT1 与多种癌症的肿瘤发生和进展有关；然而，其在前列腺癌（PCa）发生和进展中的功能和机制尚不清楚。在本研究中，我们的研究结果表明 MALAT1 在调节 PCa 增殖和葡萄糖代谢中起着关键作用。敲低 MALAT1 会影响 MYBL2 的蛋白和 mRNA 水平。此外，MALAT1 通过上调 MYBL2 增强 mTOR 通路的磷酸化水平。在 PCa 细胞系中敲低 MALAT1 或 MYBL2 可显著抑制其增殖能力。在 PCa 细胞系中沉默 MALAT1/MYBL2/mTOR 轴会影响其糖酵解和乳酸水平，我们在小鼠中验证了这些发现。此外，我们探索了 MYBL2 在 PCa 中的潜在肿瘤发生功能，发现 MYBL2 的高表达与 PCa 患者的 TNM 分期、Gleason 评分、PSA 水平和不良生存率呈正相关。综上所述，我们的研究表明 MALAT1 通过上调 MYBL2-mTOR 轴来控制癌症的葡萄糖代谢和进展。
