Laboratory of Medical Investigation, Urology Department - LIM55, University of São Paulo Medical School, São Paulo, Brazil.
Int Braz J Urol. 2013 Jan-Feb;39(1):95-101; discussion 102. doi: 10.1590/S1677-5538.IBJU.2013.01.12.
Bladder cancer (BC) is the second most common malignancy of the urinary tract, with high mortality. The knowledge of the molecular pathways associated with BC carcinogenesis is crucial to identify new diagnostic and prognostic biomarkers. MicroRNAs (miRNAs) are short non-coding RNA molecules that play important roles in the regulation of gene expression by acting directly on mRNAs. miR-145 has been considered as a tumor suppressor, which targets the c-MYC, MUC-1 and FSCN1 genes. Our aim was to evaluate the expression profile of miR-145 in low-grade non-invasive and high-grade invasive bladder urothelial carcinomas.
We studied 30 specimens of low-grade, non-invasive pTa and 30 of pT2/pT3 high-grade invasive UC obtained by transurethral resection or radical cystectomy, followed over a mean time of 16.1 months. Normal controls were represented by five samples of normal bladder biopsy from patients who underwent retropubic prostatectomy to treat BPH. miRNA extraction and cDNA generation were performed using commercial kits. Analysis was performed by qRT-PCR, and miR-145 expression was calculated using the 2-(▵▵ct) method; we used RNU-43 and RNU-48 as endogenous controls.
miR-145 was under-expressed in 73.3% and 86.7% of pTa and pT2/pT3, respectively, with expression means of 1.61 for the former and 0.66 for the last. There were no significant differences in miR-145 expression and histological grade, tumor stage, angiolymphatic neoplastic invasion and tumor recurrence.
miR-145 is under-expressed in low-grade, non-invasive and high-grade invasive urothelial bladder carcinoma and may play an important role in the carcinogenesis pathway, being an interesting candidate diagnostic marker.
膀胱癌（BC）是第二常见的泌尿道恶性肿瘤，死亡率较高。了解与膀胱癌发生相关的分子途径对于确定新的诊断和预后生物标志物至关重要。微小 RNA（miRNA）是短的非编码 RNA 分子，通过直接作用于 mRNA 来发挥重要的基因表达调控作用。miR-145 被认为是一种肿瘤抑制因子，其靶标是 c-MYC、MUC-1 和 FSCN1 基因。我们的目的是评估 miR-145 在低级别非浸润性和高级别浸润性膀胱尿路上皮癌中的表达谱。
我们研究了 30 例经尿道切除或根治性膀胱切除术获得的低级别、非浸润性 pTa 和 30 例高级别浸润性 UC 标本，平均随访时间为 16.1 个月。正常对照组由 5 例接受耻骨后前列腺切除术治疗 BPH 的患者的正常膀胱活检样本组成。使用商业试剂盒进行 miRNA 提取和 cDNA 生成。通过 qRT-PCR 进行分析，并使用 2-（△△ct）方法计算 miR-145 表达；我们使用 RNU-43 和 RNU-48 作为内参。
pTa 和 pT2/pT3 中 miR-145 的表达分别下调了 73.3%和 86.7%，前者的表达均值为 1.61，后者为 0.66。miR-145 表达与组织学分级、肿瘤分期、血管淋巴管肿瘤侵犯和肿瘤复发均无显著差异。
miR-145 在低级别、非浸润性和高级别浸润性尿路上皮膀胱癌中表达下调，可能在致癌途径中发挥重要作用，是一种有前途的诊断标志物候选者。
