Long Noncoding RNA Cancer Susceptibility Candidate 8 Suppresses the Proliferation of Bladder Cancer Cells via Regulating Glycolysis

Long Noncoding RNA Cancer Susceptibility Candidate 8 Suppresses the Proliferation of Bladder Cancer Cells via Regulating Glycolysis
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DOI:
10.1089/dna.2017.3785
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发表时间:
2017-09-01
影响因子:
3.1
通讯作者:
Duan, Liangbin
Duan, Liangbin
中科院分区:
生物学4区
文献类型:
--
作者:
Hu, Renguang;Zhong, Peng;Duan, Liangbin

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越来越多的证据表明长链非编码RNA(lncRNA)在肿瘤发生中的重要调控作用。膀胱癌已成为最常见的泌尿系统恶性肿瘤,这是常见的诊断在成年人中。在这项研究中,我们发现lncRNA癌症易感性候选者8(CASC 8)在膀胱癌中显著下调,并与膀胱癌患者的晚期相关。过表达CASC 8可显著抑制膀胱癌细胞增殖。从机制上讲,我们说明了CASC 8通过与成纤维细胞生长因子受体1(FGFR 1)相互作用减少膀胱癌细胞的糖酵解。CASC8与FGFR1的结合抑制FGFR1介导的乳酸脱氢酶A磷酸化,其减弱丙酮酸转化为乳酸。总的来说,我们的研究结果揭示了CASC 8在膀胱肿瘤发生中的关键作用,并表明CASC 8可能作为诊断膀胱癌的候选生物标志物。
Increasing evidence highlights the critical regulatory role of long noncoding RNAs (lncRNAs) in carcinogenesis. Bladder cancer has become the most prevalent urologic malignancy, which is commonly diagnosed among adults. In this study, we showed that the lncRNA cancer susceptibility candidate 8 (CASC8) is significantly downregulated in bladder cancers and associated with the advanced stage of bladder cancer patients. Overexpression of CASC8 remarkably suppressed the bladder cancer cell proliferation. Mechanistically, we illustrated that CASC8 reduced the glycolysis of bladder cancer cells via interacting with the fibroblast growth factor receptor 1 (FGFR1). The binding of CASC8 with FGFR1 inhibits FGFR1-mediated lactate dehydrogenase A phosphorylation, which attenuates the conversion of pyruvate into lactate. Collectively, our findings uncovered the pivotal role of CASC8 in bladder tumorigenesis and suggested that CASC8 may function as a candidate biomarker for the diagnosis of bladder cancer.