title: MicroRNAs and epithelial-mesenchymal transition in prostate cancer.
abstract: 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.
authors: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, CA, USA.
authors: Kirandeep
authors: K
authors: Sekhon
authors: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, CA, USA.
authors: Nathan
authors: N
authors: Bucay
authors: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, CA, USA.
authors: Shahana
authors: S
authors: Majid
authors: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, CA, USA.
authors: Rajvir
authors: R
authors: Dahiya
authors: Department of Urology, Veterans Affairs Medical Center, San Francisco and University of California San Francisco, CA, USA.
authors: Sharanjot
authors: S
authors: Saini
mesh_terms: D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D008297:Male; D035683:MicroRNAs; D009361:Neoplasm Invasiveness / Q000235:genetics; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D035683:MicroRNAs
keywords: EMT; metastasis; microRNAs; prostate cancer; recurrence