Gottardo Fedra, Liu Chang Gong, Ferracin Manuela, Calin George A, Fassan Matteo, Bassi Pierfrancesco, Sevignani Cinzia, Byrne Dolores, Negrini Massimo, Pagano Francesco, Gomella Leonard G, Croce Carlo M, Baffa Raffaele
Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Urol Oncol. 2007 Sep-Oct;25(5):387-92. doi: 10.1016/j.urolonc.2007.01.019.
Micro-RNAs are a group of small noncoding RNAs with modulator activity of gene expression. Recently, micro-RNA genes were found abnormally expressed in several types of cancers. To study the role of the micro-RNAs in human kidney and bladder cancer, we analyzed the expression profile of 245 micro-RNAs in kidney and bladder primary tumors.
A total of 27 kidney specimens (20 carcinomas, 4 benign renal tumors, and 3 normal parenchyma) and 27 bladder specimens (25 urothelial carcinomas and 2 normal mucosa) were included in the study. Total RNA was used for hybridization on an oligonucleotide microchip for micro-RNA profiling developed in our laboratories. This microchip contains 368 probes in triplicate, corresponding to 245 human and mouse micro-RNA genes.
A set of 4 human micro-RNAs (miR-28, miR-185, miR-27, and let-7f-2) were found significantly up-regulated in renal cell carcinoma (P < 0.05) compared to normal kidney. Human micro-RNAs miR-223, miR-26b, miR-221, miR-103-1, miR-185, miR-23b, miR-203, miR-17-5p, miR-23a, and miR-205 were significantly up-regulated in bladder cancers (P < 0.05) compared to normal bladder mucosa. Of the kidney cancers studied, there was no differential micro-RNA expression across various stages, whereas with increasing tumor-nodes-metastasis staging in bladder cancer, miR-26b showed a moderate decreasing trend (P = 0.082).
Our results show that different micro-RNAs are deregulated in kidney and bladder cancer, suggesting the involvement of these genes in the development and progression of these malignancies. Further studies are needed to clarify the role of micro-RNAs in neoplastic transformation and to test the potential clinical usefulness of micro-RNAs microarrays as diagnostic and prognostic tool.
微小RNA是一类具有基因表达调节活性的小型非编码RNA。最近，人们发现微小RNA基因在几种癌症中异常表达。为了研究微小RNA在人类肾癌和膀胱癌中的作用，我们分析了245种微小RNA在肾脏和膀胱原发性肿瘤中的表达谱。
本研究共纳入27份肾脏标本（20例癌、4例良性肾肿瘤和3例正常实质）和27份膀胱标本（25例尿路上皮癌和2例正常黏膜）。总RNA用于在我们实验室开发的用于微小RNA谱分析的寡核苷酸微芯片上进行杂交。该微芯片包含一式三份的368个探针，对应于245个人类和小鼠微小RNA基因。
与正常肾脏相比，发现一组4种人类微小RNA（miR-28、miR-185、miR-27和let-7f-2）在肾细胞癌中显著上调（P < 0.05）。与正常膀胱黏膜相比，人类微小RNA miR-223、miR-26b、miR-221、miR-103-1、miR-185、miR-23b、miR-203、miR-17-5p、miR-23a和miR-205在膀胱癌中显著上调（P < 0.05）。在所研究的肾癌中，不同阶段的微小RNA表达没有差异，而在膀胱癌中，随着肿瘤-淋巴结-转移分期增加，miR-26b呈中度下降趋势（P = 0.082）。
我们的结果表明，不同的微小RNA在肾癌和膀胱癌中失调，提示这些基因参与了这些恶性肿瘤的发生和发展。需要进一步研究以阐明微小RNA在肿瘤转化中的作用，并测试微小RNA微阵列作为诊断和预后工具的潜在临床实用性。
