TY - JOUR
T1 - MicroRNAs and epithelial-mesenchymal transition in prostate cancer
AU - Sekhon, Kirandeep
AU - Bucay, Nathan
AU - Majid, Shahana
AU - Dahiya, Rajvir
AU - Saini, Sharanjot
PY - 2016
Y1 - 2016
N2 - 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. Epithelialmesenchymal 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 EMTinhibiting 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.
AB - 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. Epithelialmesenchymal 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 EMTinhibiting 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.
KW - EMT
KW - Metastasis
KW - MicroRNAs
KW - Prostate cancer
KW - Recurrence
UR - http://www.scopus.com/inward/record.url?scp=84993982657&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84993982657&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.11708
DO - 10.18632/oncotarget.11708
M3 - Review article
C2 - 27588490
AN - SCOPUS:84993982657
SN - 1949-2553
VL - 7
SP - 67597
EP - 67611
JO - Oncotarget
JF - Oncotarget
IS - 41
ER -