MicroRNAs and epithelial-mesenchymal transition in prostate cancer.
MicroRNAs and epithelial-mesenchymal transition in prostate cancer.
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DOI：
10.18632/oncotarget.11708
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发表时间：
2016-10-11
期刊：
影响因子：
--
通讯作者：
Saini S
中科院分区：
文献类型：
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作者：
Sekhon K;Bucay N;Majid S;Dahiya R;Saini S
前列腺癌(PCA)是男性癌症相关死亡的主要原因。相当一部分的前列腺癌侵袭性很强，常常转移到骨，导致相当大的发病率和死亡率。此外，前列腺癌与高复发率有关，这通常归因于癌症干细胞的存在。上皮-间充质转化(EMT)是一种以上皮基因表达降低、间质基因表达增加为特征的过程，在肿瘤的侵袭、转移和复发中起着关键作用。在PCa中，EMT尤其与转移性疾病有关，并且microRNAs已成为PCa EMT的关键转录后调节因子。在本文中，我们综述了miRNAs在前列腺癌EMT中的作用，它在进展、转移和复发中起作用。到目前为止的研究表明，microRNA通过多种机制介导对PCa EMT的有效和可逆的控制，包括：(I)直接抑制单个或多个EMT-TF或调节细胞骨架成分(上皮/间充质基因)或(Ii)调节参与EMT的关键信号通路。致癌的microRNA通常通过抑制上皮特性作为EMT的促进剂，而抑制肿瘤的miRNAs通过抑制间充质进展而发挥作用。此外，EMT在机制上与PCa中的干细胞签名有关，据报道，与EMT有关的几个miRNAs可以影响PCa干细胞。EMT抑制miRNAs的丢失和/或EMT促进miRNAs的获得会导致PCa EMT的诱导，导致肿瘤的进展、转移和复发。恢复肿瘤抑制miRNAs的表达和抑制致癌miRNAs的表达是预防疾病转移和复发的潜在治疗机会。
Prostate cancer (PCa) is a leading cause of male cancer-related deaths. A significant fraction of prostate tumors are very aggressive, often metastasizing to bone, causing significant morbidity and mortality. Also, PCa is associated with high rates of recurrence, often attributed to the existence of cancer stem cells. Epithelial-mesenchymal transition (EMT), a process characterized by decreased expression of epithelial genes and increased expression of mesenchymal genes, plays a critical role in tumor invasion, metastasis and recurrence. In PCa, EMT has been implicated particularly in the context of metastatic disease and microRNAs have emerged as critical post-transcriptional regulators of PCa EMT. In this review, we summarize the role of miRNAs in PCa EMT that play a role in progression, metastasis and recurrence. Studies till date suggest that microRNAs mediate efficient and reversible control of PCa EMT via multiple mechanisms including either by (i) directly repressing single or multiple EMT-TFs or regulating cytoskeletal components (epithelial/mesenchymal genes) or (ii) regulating key signaling pathways involved in EMT. Oncogenic microRNAs often act as EMT promoters by repressing epithelial characteristics and tumor suppressive miRNAs act by inhibiting mesenchymal progression. Further, EMT is mechanistically linked to stem cell signatures in PCa and several miRNAs implicated in EMT have been reported to influence PCa stem cells. Loss of EMT-inhibiting miRNAs and/or gain of EMT promoting miRNAs lead to induction of PCa EMT, leading to tumor progression, metastasis and recurrence. Restoring expression of tumor suppressive miRNAs and inhibiting oncogenic miRNAs represent potential therapeutic opportunities to prevent disease metastasis and recurrence.