Li Yongzhi, Shi Benkang, Dong Fengming, Zhu Xingwang, Liu Bing, Liu Yili
Department of Urology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
Front Genet. 2019 Mar 29;10:280. doi: 10.3389/fgene.2019.00280. eCollection 2019.
Although accumulating evidence has shown the important function of long non-coding RNAs (lncRNAs) in tumor progression and chemotherapy resistance, the role of lncRNA DLEU1 in regulating proliferation, invasion, and chemoresistance of bladder cancer (BCA) cells remains largely unknown. Here, we found that DLEU1 was upregulated in BLCA tissues and BCA patients with high DLEU1 expression exhibited a shorter survival time. Furthermore, mechanistic analysis and functional assays validated that DLEU1 induced cell proliferation, invasion, and cisplatin resistance of BCA cells by de-repressing the expression of HS3ST3B1 through sponging miR-99b. Low miR-99b and high HS3ST3B1 levels were correlated with worse prognosis in patients with BCA. Ectopic expression of HS3ST3B1 or inhibition of miR-99b reversed DLEU1 knockdown-mediated suppression of cell proliferation, invasion, and cisplatin resistance. Thus, our study revealed a novel role for the DLEU1/miR-99b/HS3ST3B1 axis in regulating proliferation, invasion, and cisplatin resistance of BCA cells.
尽管越来越多的证据表明长链非编码RNA（lncRNAs）在肿瘤进展和化疗耐药中具有重要作用，但lncRNA DLEU1在调节膀胱癌（BCA）细胞增殖、侵袭和化疗耐药中的作用仍 largely未知。在此，我们发现DLEU1在BLCA组织中上调，且DLEU1表达高的BCA患者生存时间较短。此外，机制分析和功能试验证实，DLEU1通过海绵吸附miR-99b解除对HS3ST3B1表达的抑制，从而诱导BCA细胞增殖、侵袭和顺铂耐药。低miR-99b水平和高HS3ST3B1水平与BCA患者的不良预后相关。HS3ST3B1的异位表达或miR-99b的抑制可逆转DLEU1敲低介导的对细胞增殖、侵袭和顺铂耐药的抑制。因此，我们的研究揭示了DLEU1/miR-99b/HS3ST3B1轴在调节BCA细胞增殖、侵袭和顺铂耐药中的新作用。
