Zheng Dandan, Huang Xianxian, Peng Juanfei, Zhuang Yanyan, Li Yuanhua, Qu Junchi, Zhang Shineng, Huang Fengting
Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
Cell Death Discov. 2021 Nov 22;7(1):362. doi: 10.1038/s41420-021-00759-8.
Emerging evidence has demonstrated that circular RNAs (circRNAs) take part in the initiation and development of pancreatic ductal adenocarcinoma (PDA), a deadly neoplasm with an extremely low 5-year survival rate. Reprogrammed glucose metabolism is a key feature of tumour development, including PDA. In this research, we evaluated the role of circRNAs in reprogrammed glucose metabolism in PDA. RNA sequencing under various glucose incubation circumstances was performed. A new circMYOF was identified. Sanger sequencing and RNase R treatment confirmed its circular RNA characteristics. Real-time PCR indicated that it was highly expressed in PDA clinical specimens and cell lines. Gain-of- and loss-of-function assays showed that circMYOF induced progression in PDA. Mechanistically, RNA pull-down and luciferase reporter experiments elucidated that circMYOF, as a competing endogenous RNA for miR-4739, facilitated glycolysis via the VEGFA/PI3K/AKT pathway. Taken together, our findings indicate that circMYOF may work as a desirable biomarker and therapeutic target for PDA patients.
新出现的证据表明，环状RNA（circRNAs）参与了胰腺导管腺癌（PDA）的发生和发展，PDA是一种致命的肿瘤，5年生存率极低。重编程的葡萄糖代谢是肿瘤发展的一个关键特征，包括PDA。在本研究中，我们评估了circRNAs在PDA重编程葡萄糖代谢中的作用。在各种葡萄糖孵育条件下进行了RNA测序。鉴定出一种新的circMYOF。桑格测序和RNase R处理证实了其环状RNA特征。实时PCR表明，它在PDA临床标本和细胞系中高表达。功能获得和功能丧失试验表明，circMYOF诱导PDA进展。机制上，RNA下拉和荧光素酶报告实验表明，circMYOF作为miR-4739的竞争性内源性RNA，通过VEGFA/PI3K/AKT途径促进糖酵解。综上所述，我们的研究结果表明，circMYOF可能作为PDA患者理想的生物标志物和治疗靶点。
