Laboratory for Translational Oncology and Personalized Medicine, Rashid Latif Medical College, Lahore, Pakistan.
Immunogenetics. 2013 May;65(5):315-32. doi: 10.1007/s00251-012-0677-2. Epub 2013 Apr 5.
Oncogenic fusion proteins belong to an important class that disrupts gene expression networks in a cell. Astonishingly, fusion-positive prostate cancer cells enable the multi-gene regulatory capability of miRNAs to remodel the signal transduction landscape, enhancing or antagonizing the transmission of information to downstream effectors. Accumulating evidence substantiates the fact that miRNAs translate into dose-dependent responsiveness of cells to signaling regulators in transmembrane protease serine 2:ETS-related gene (TMPRSS2-ERG)-positive cells. Wide ranging signaling proteins are the targets for the degree of quantitative fluctuations imposed by miRNAs. miRNA signatures are aberrantly expressed in fusion-positive cancer cells, suggesting that they have a cumulative effect on tumor aggressiveness. It seems attractive to note that TMPRSS2:ERG fusion has a stronger effect as tumors positive for the oncogenic TMPRSS2:ERG have dysregulated oncomirs and tumor suppressor miRNA signature. It is undeniable that a comprehensive analysis of the prostate cancer microRNAome is necessary to uncover novel microRNAs and pathways associated with prostate cancer. Moreover, the identification and validation of miRNA signature in TMPRSS2-ERG-positive prostate cancer cells may help to identify novel molecular targets and pathways for personalized therapy.
致癌融合蛋白属于一类重要的蛋白，它们会破坏细胞中的基因表达网络。令人惊讶的是，融合阳性前列腺癌细胞使 miRNA 的多基因调控能力能够重塑信号转导景观，增强或拮抗信息向下游效应物的传递。越来越多的证据证实了这样一个事实，即 miRNA 将转化为细胞对跨膜蛋白酶丝氨酸 2：ETS 相关基因（TMPRSS2-ERG）阳性细胞中信号转导调节剂的剂量依赖性反应。广泛存在的信号蛋白是 miRNA 施加的定量波动程度的靶标。miRNA 特征在融合阳性癌细胞中异常表达，表明它们对肿瘤侵袭性有累积效应。值得注意的是，TMPRSS2:ERG 融合的作用更强，因为阳性肿瘤的致癌 TMPRSS2:ERG 具有失调的癌 miRNA 和肿瘤抑制 miRNA 特征。不可否认的是，需要对前列腺癌 microRNAome 进行全面分析，以揭示与前列腺癌相关的新的 microRNAs 和途径。此外，鉴定和验证 TMPRSS2-ERG 阳性前列腺癌细胞中的 miRNA 特征可能有助于确定新的分子靶点和个性化治疗途径。
