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Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients.
Cancer Medicine ( IF 2.9 ) Pub Date : 2020-04-06 , DOI: 10.1002/cam4.3006
Chong Shen 1, 2 , Zhouliang Wu 1, 2 , Yujie Wang 1, 2 , Shen Gao 1, 2 , La Da 1, 2 , Linguo Xie 1, 2 , Yunkai Qie 1, 2 , Dawei Tian 1, 2 , Hailong Hu 1, 2
Affiliation  

Growing evidence has indicated that circular RNAs (circRNAs) play crucial roles in multiple biological processes. However, alterations in circRNA profiles during bladder cancer progression and the clinical significance thereof remain unclear. Therefore, high‐throughput RNA sequencing was conducted to identify circRNA and mRNA profiles in five pairs of bladder cancer tissues and adjacent noncancerous tissues. A total of 87 differentially expressed circRNAs and 2756 mRNAs were detected in above bladder cancer samples compared with paired noncancerous samples. Functional enrichment analyses, circRNA‐microRNA‐mRNA, and protein‐protein interaction networks revealed that these dysregulated circRNAs were potentially involved in carcinogenesis and evolution of bladder cancer. Subsequently, the differential expression of eight circRNAs was detected by real‐time qPCR. Hsa_circ_0003141 and hsa_circ_0008039 were significantly upregulated as well as hsa_circ_0026782, hsa_circ_0077837, hsa_circ_0004826, and hsa_circ_0001946 were significantly downregulated among validation of 70 matched bladder cancer tissues (≥75%). Moreover, hsa_circ_0077837 and hsa_circ_0004826 were also verified as markedly downregulated in four bladder cancer cells (100%). Naturally, hsa_circ_0077837 and hsa_circ_0004826 were also demonstrated using RNase‐R+ resistance experiments. In addition, Fisherʹs exact test, Kaplan‐Meier plots, Cox regression analyses, and receiver operating characteristic curve was performed to assess their clinical value. Downregulation of hsa_circ_0077837 and hsa_circ_0004826 all was significantly correlated with worse clinicopathological features and poor prognosis of bladder cancer patients. The area under the receiver operating characteristic curve of them was 0.775 (P  < .0001) and 0.790 (P  < .0001), respectively. Not surprisingly, in vitro functional experiments also demonstrated that the overexpression of hsa_circ_0077837 and hsa_circ_0004826 significantly weakened the proliferation, migration, and invasion of bladder cancer cells. Overall, hsa_circ_0077837 and hsa_circ_0004826 might act as tumor suppressors in the bladder cancer progression and serve as a potential biomarker for the diagnosis, prognosis, and therapy of bladder cancer.

中文翻译:

下调hsa_circ_0077837和hsa_circ_0004826有助于膀胱癌的发展,并预测膀胱癌患者的预后不良。

越来越多的证据表明,环状RNA(circRNA)在多种生物学过程中起着至关重要的作用。然而,尚不清楚在膀胱癌进展期间circRNA谱的改变及其临床意义。因此,进行了高通量RNA测序,以鉴定五对膀胱癌组织和相邻非癌组织中的circRNA和mRNA谱。与配对的非癌样品相比,在上述膀胱癌样品中总共检测到87个差异表达的circRNA和2756 mRNA。功能富集分析,circRNA-microRNA-mRNA和蛋白质-蛋白质相互作用网络显示,这些失调的circRNA可能与膀胱癌的发生和发展有关。后来,实时定量PCR检测了八个circRNA的差异表达。在70个匹配的膀胱癌组织(≥75%)的验证中,hsa_circ_0003141和hsa_circ_0008039显着上调,而hsa_circ_0026782,hsa_circ_0077837,hsa_circ_0004826和hsa_circ_0001946则显着下调。此外,还证实了hsa_circ_0077837和hsa_circ_0004826在四个膀胱癌细胞(100%)中均显着下调。当然,也使用RNase-R +抗性实验证明了hsa_circ_0077837和hsa_circ_0004826。此外,还进行了Fisher精确检验,Kaplan-Meier图,Cox回归分析和接收器工作特征曲线,以评估其临床价值。hsa_circ_0077837和hsa_circ_0004826的下调均与较差的临床病理特征和膀胱癌患者的不良预后密切相关。它们的接收器工作特性曲线下方的面积为0.775(P  <.0001)和0.790(P  <.0001)。毫不奇怪,体外功能实验还表明,hsa_circ_0077837和hsa_circ_0004826的过表达显着削弱了膀胱癌细胞的增殖,迁移和侵袭。总体而言,hsa_circ_0077837和hsa_circ_0004826可能在膀胱癌的发展过程中起抑癌作用,并可能成为诊断,预后和治疗膀胱癌的潜在生物标记。
更新日期:2020-04-06
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