Guo Jinan, Zhao Pan, Liu Zengqin, Li Zaishang, Yuan Yeqing, Zhang Xueqi, Yu Zhou, Fang Jiequn, Xiao Kefeng
Department of Urology, Shenzhen Urology Minimally Invasive Engineering Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, The First Affiliated Hospital of South University of Science and Technology of China, Shenzhen, China.
Shenzhen Public Service Platform on Tumor Precision Medicine and Molecular Diagnosis, Shenzhen Urology Minimally Invasive Engineering Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, The First Affiliated Hospital of South University of Science and Technology of China, Shenzhen, China.
Front Oncol. 2019 Nov 29;9:1242. doi: 10.3389/fonc.2019.01242. eCollection 2019.
MicroRNAs (miRNAs) are endogenous non-coding RNAs that negatively regulate the expression of downstream targeted mRNAs. Increasing evidence has suggested that miRNAs act as tumor suppressors or oncogenes to interfere the progression of cancers. Here, we showed that miR-204-3p was decreased in bladder cancer tissues and cell lines. Down-regulation of miR-204-3p was significantly associated with a poor prognosis in bladder cancer patients. Overexpression of miR-204-3p inhibited proliferation and induced apoptosis in bladder cancer cells. Furthermore, miR-204-3p was found to bind to the 3'-untranslated region (UTR) of the lactate dehydrogenase (LDHA), which consequently reduced the expression of both mRNA and protein of LDHA. Interestingly, overexpression of miR-204-3p decreased glucose consumption and lactate production of bladder cancer cells. Overexpression of LDHA relieved the growth inhibition and cell apoptosis enhancement by miR-204-3p in bladder cancer cells. These results demonstrated that miR-204-3p negatively modulated the proliferation of bladder cancer cells via targeting LDHA-mediated glycolysis. MiR-204-3p might be a promising candidate for designing anticancer medication.
微小RNA(miRNA)是内源性非编码RNA,可负向调节下游靶向mRNA的表达。越来越多的证据表明,miRNA作为肿瘤抑制因子或癌基因参与干扰癌症的进展。在此,我们发现miR-204-3p在膀胱癌组织和细胞系中表达降低。miR-204-3p的下调与膀胱癌患者的不良预后显著相关。miR-204-3p的过表达抑制了膀胱癌细胞的增殖并诱导其凋亡。此外,发现miR-204-3p与乳酸脱氢酶(LDHA)的3'非翻译区(UTR)结合,从而降低了LDHA的mRNA和蛋白表达。有趣的是,miR-204-3p的过表达降低了膀胱癌细胞的葡萄糖消耗和乳酸生成。LDHA的过表达缓解了miR-204-3p对膀胱癌细胞生长的抑制作用并增强了细胞凋亡。这些结果表明,miR-204-3p通过靶向LDHA介导的糖酵解负向调节膀胱癌细胞的增殖。miR-204-3p可能是设计抗癌药物的一个有前景的候选分子。