MicroRNA-23b functions as a tumor suppressor by regulating Zeb1 in bladder cancer.
MicroRNA-23b functions as a tumor suppressor by regulating Zeb1 in bladder cancer.
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DOI：
10.1371/journal.pone.0067686
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yamamura S
中科院分区：
文献类型：
--
作者：
Majid S;Dar AA;Saini S;Deng G;Chang I;Greene K;Tanaka Y;Dahiya R;Yamamura S
MicroRNAs （miRNAs）是一种小的非编码rna，通过靶向抑制转录和翻译来调节基因表达。在这项研究中，我们发现miRNA-23b （miR-23b）在膀胱癌中起肿瘤抑制作用。实时荧光定量PCR分析显示，miR-23b在膀胱癌细胞系和肿瘤组织中较非恶性细胞和正常组织样本明显下调。我们还证明miR-23b表达有可能成为膀胱癌的诊断和预后生物标志物。Kaplan-Meier分析显示，miR-23b高表达与膀胱癌患者较高的总生存率呈正相关。ROC分析显示miR-23b表达可以区分正常和膀胱癌组织。我们进一步阐明了miR-23b在膀胱癌中的生物学意义。膀胱癌细胞中过表达miR-23b可抑制细胞增殖，损害集落形成。荧光活化细胞分选（FACS）分析显示，在膀胱癌细胞中重新表达miR-23b可诱导G0/G1细胞周期阻滞和凋亡，同时抑制细胞迁移和侵袭。荧光素酶报告基因试验表明，Zeb1是上皮细胞向间质转化（EMT）的关键调节因子，是miR-23b在膀胱癌中的直接靶点。这些结果表明，miR-23b的缺失具有增殖优势，促进膀胱癌细胞的迁移和侵袭。此外，重新表达miR-23b可能是治疗人类膀胱癌的一种有益的治疗策略。
MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation. In this study we show that miRNA-23b (miR-23b) acts as a tumor suppressor in bladder cancer. Quantitative real-time PCR analysis showed that miR-23b is significantly down-regulated in bladder cancer cell lines and tumor tissues compared to non-malignant cells and normal tissue samples. We also demonstrate that miR-23b expression has a potential to be diagnostic and prognostic biomarker in bladder cancer. High miR-23b expression is positively correlated with higher overall survival of bladder cancer patients as revealed by Kaplan-Meier analysis. ROC analysis showed that miR-23b expression can distinguish between normal and bladder cancer tissues. Further we elucidated the biological significance of miR-23b in bladder cancer. Over-expression of miR-23b in bladder cancer cells inhibited cell proliferation and impaired colony formation. Fluorescence activated cell sorting (FACS) analysis revealed that re-expression of miR-23b in bladder cancer cells induced G0/G1 cell cycle arrest and apoptosis while inhibiting cell migration and invasion. Luciferase reporter assays demonstrated that Zeb1, a crucial regulator of epithelial-to-mesenchymal transition (EMT), is a direct target of miR-23b in bladder cancer. These results show that loss of miR-23b confers a proliferative advantage and promotes bladder cancer cell migration and invasion. Furthermore, re-expression of miR-23b may be a beneficial therapeutic strategy for the treatment of human bladder cancer.
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影响因子：
3.7
作者：
Majid S;Dar AA;Saini S;Shahryari V;Arora S;Zaman MS;Chang I;Yamamura S;Chiyomaru T;Fukuhara S;Tanaka Y;Deng G;Tabatabai ZL;Dahiya R
通讯作者：
Dahiya R
影响因子：
11.2
作者：
Alonso, Soledad R.;Tracey, Lorraine;Rodriguez-Peralto, Jose L.
通讯作者：
Rodriguez-Peralto, Jose L.
影响因子：
29.4
作者：
Spaderna, Simone;Schmalhofer, Otto;Brabletz, Thomas
通讯作者：
Brabletz, Thomas
DOI：
10.1158/1940-6207.capr-11-0267
发表时间：
2011-10
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Saini S;Arora S;Majid S;Shahryari V;Chen Y;Deng G;Yamamura S;Ueno K;Dahiya R
通讯作者：
Dahiya R
影响因子：
11.2
作者：
Sempere, Lorenzo F.;Christensen, Mette;Cole, Charles N.
通讯作者：
Cole, Charles N.