Expression of tumor suppressive microRNA-34a is associated with a reduced risk of bladder cancer recurrence.
Expression of tumor suppressive microRNA-34a is associated with a reduced risk of bladder cancer recurrence.
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DOI：
10.1002/ijc.29413
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发表时间：
2015-09-01
影响因子：
6.4
通讯作者：
Sempere, Lorenzo F.
中科院分区：
文献类型：
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作者：
Andrew, Angeline S.;Marsit, Carmen J.;Schned, Alan R.;Seigne, John D.;Kelsey, Karl T.;Moore, Jason H.;Perreard, Laurent;Karagas, Margaret R.;Sempere, Lorenzo F.
膀胱癌是美国男性中第四常见的癌症，超过一半的患者在初次诊断后5年内复发。需要复发性膀胱癌表型的其他临床信息和可操作的生物标志物来改善用于复发预防的筛查和分子治疗方法。microRNA-34 a（miR-34 a）是一种短的非编码调控RNA，具有肿瘤抑制特性。我们利用我们在美国新罕布什尔州进行的独特的、大规模的、基于人群的膀胱癌预后研究来评估单个肿瘤细胞中的miR-34 a表达水平，以评估预后价值。我们收集了详细的暴露和病史数据，以及膀胱患者的肿瘤组织标本，并长期随访复发，进展和生存。对尿路上皮癌组织标本（n=229）进行基于荧光素的原位杂交检测。与肌肉侵袭性肿瘤相比，更大比例的非肌肉侵袭性肿瘤的癌细胞内具有高水平的miR-34 a。基线非肌肉浸润性肿瘤中miR-34 a水平高的患者复发风险较低（校正风险比（HR）0.57 95%CI 0.34-0.93）。与这些观察结果一致，我们证明了miR-34 a在培养的尿路上皮细胞中的功能性肿瘤抑制作用，包括减少基质胶侵袭和在软琼脂中的生长。我们的研究结果强调了需要进一步的临床研究miR-34 a作为复发筛查的指导，并作为膀胱中可能的候选治疗靶点。
Bladder cancer is the 4th most common cancer among men in the U.S. and more than half of patients experience recurrences within 5 years after initial diagnosis. Additional clinically informative and actionable biomarkers of the recurrent bladder cancer phenotypes are needed to improve screening and molecular therapeutic approaches for recurrence prevention. MicroRNA-34a (miR-34a) is a short non-coding regulatory RNA with tumor suppressive attributes. We leveraged our unique, large, population-based prognostic study of bladder cancer in New Hampshire, U.S. to evaluate miR-34a expression levels in individual tumor cells to assess prognostic value. We collected detailed exposure and medical history data, as well as tumor tissue specimens from bladder patients and followed them long-term for recurrence, progression and survival. Fluorescence-based in situ hybridization assays were performed on urothelial carcinoma tissue specimens (n=229). A larger proportion of the non-muscle invasive tumors had high levels of miR-34a within the carcinoma cells compared to those tumors that were muscle invasive. Patients with high miR-34a levels in their baseline non-muscle invasive tumors experienced lower risks of recurrence (adjusted hazard ratio (HR) 0.57 95%CI 0.34–0.93). Consistent with these observations, we demonstrated a functional tumor suppressive role for miR-34a in cultured urothelial cells, including reduced matrigel invasion and growth in soft agar. Our results highlight the need for further clinical studies of miR-34a as a guide for recurrence screening and as a possible candidate therapeutic target in the bladder.
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捕获microRNA结合的mRNA将肿瘤抑制器miR-34a识别为生长因子信号传导的调节剂。
影响因子：
4.5
作者：
Lal A;Thomas MP;Altschuler G;Navarro F;O'Day E;Li XL;Concepcion C;Han YC;Thiery J;Rajani DK;Deutsch A;Hofmann O;Ventura A;Hide W;Lieberman J
通讯作者：
Lieberman J
影响因子：
3.7
作者：
Penumutchu SR;Chou RH;Yu C
通讯作者：
Yu C
影响因子：
14.9
作者：
Gonzalgo, ML;Jones, PA
通讯作者：
Jones, PA
影响因子：
64.8
作者：
He, Lin;He, Xingyue;Hannon, Gregory J.
通讯作者：
Hannon, Gregory J.
影响因子：
8.8
作者：
通讯作者：
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