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miR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes the development of castration resistance.
Oncogene. 2017 11 09; 36(45):6336-6347.O

Abstract

Clinical intervention for patients with advanced prostate cancer (PCa) remains challenging due to the inevitable recurrence of castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT). Cancer stem cells (CSCs) with serial tumor-propagating capacity are considered to be the driving force for PCa progression and recurrence. In this study, we report that the miR-302/367 cluster, a previously identified potent pluripotency regulator, is upregulated in prostate tumors. Specifically, the forced expression of the miR-302/367 cluster accelerates the in vitro and in vivo growth of PCa cells and their resistance to androgen ablation, whereas the knockdown of the miR-302/367 cluster using anti-sense RNA suppresses the incidence of formation, growth rate and endpoint weight of PCa cell tumors. Mechanistically, we find that LATS2, a key component of the tumor-suppressive Hippo signaling pathway, acts as a direct target of the miR-302/367 cluster in PCa cells. The downregulation of LATS2 by the miR-302/367 cluster reduces the phosphorylation and enhances the nuclear translocation of the YAP oncoprotein. Conversely, the restoration of LATS2 expression abrogates the tumor-promoting effects of forced miR-302/367 cluster expression. Collectively, the potent pluripotency regulator-triggered miR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes castration resistance. Thus, targeting this signaling axis may represent a promising therapeutic strategy for CRPC.

Authors+Show Affiliations

State Key Laboratory of Oncogenes and Related Genes, Ren ji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Oncogenes and Related Genes, Ren ji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Oncogenes and Related Genes, Ren ji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Oncogenes and Related Genes, Ren ji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.State Key Laboratory of Oncogenes and Related Genes, Ren ji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Oncogenes and Related Genes, Ren ji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Oncogenes and Related Genes, Ren ji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28745315

Citation

Guo, Y, et al. "MiR-302/367/LATS2/YAP Pathway Is Essential for Prostate Tumor-propagating Cells and Promotes the Development of Castration Resistance." Oncogene, vol. 36, no. 45, 2017, pp. 6336-6347.
Guo Y, Cui J, Ji Z, et al. MiR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes the development of castration resistance. Oncogene. 2017;36(45):6336-6347.
Guo, Y., Cui, J., Ji, Z., Cheng, C., Zhang, K., Zhang, C., Chu, M., Zhao, Q., Yu, Z., Zhang, Y., Fang, Y. X., Gao, W. Q., & Zhu, H. H. (2017). MiR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes the development of castration resistance. Oncogene, 36(45), 6336-6347. https://doi.org/10.1038/onc.2017.240
Guo Y, et al. MiR-302/367/LATS2/YAP Pathway Is Essential for Prostate Tumor-propagating Cells and Promotes the Development of Castration Resistance. Oncogene. 2017 11 9;36(45):6336-6347. PubMed PMID: 28745315.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - miR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes the development of castration resistance. AU - Guo,Y, AU - Cui,J, AU - Ji,Z, AU - Cheng,C, AU - Zhang,K, AU - Zhang,C, AU - Chu,M, AU - Zhao,Q, AU - Yu,Z, AU - Zhang,Y, AU - Fang,Y-X, AU - Gao,W-Q, AU - Zhu,H H, Y1 - 2017/07/24/ PY - 2016/10/17/received PY - 2017/05/14/revised PY - 2017/06/08/accepted PY - 2017/7/27/pubmed PY - 2017/12/2/medline PY - 2017/7/27/entrez SP - 6336 EP - 6347 JF - Oncogene JO - Oncogene VL - 36 IS - 45 N2 - Clinical intervention for patients with advanced prostate cancer (PCa) remains challenging due to the inevitable recurrence of castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT). Cancer stem cells (CSCs) with serial tumor-propagating capacity are considered to be the driving force for PCa progression and recurrence. In this study, we report that the miR-302/367 cluster, a previously identified potent pluripotency regulator, is upregulated in prostate tumors. Specifically, the forced expression of the miR-302/367 cluster accelerates the in vitro and in vivo growth of PCa cells and their resistance to androgen ablation, whereas the knockdown of the miR-302/367 cluster using anti-sense RNA suppresses the incidence of formation, growth rate and endpoint weight of PCa cell tumors. Mechanistically, we find that LATS2, a key component of the tumor-suppressive Hippo signaling pathway, acts as a direct target of the miR-302/367 cluster in PCa cells. The downregulation of LATS2 by the miR-302/367 cluster reduces the phosphorylation and enhances the nuclear translocation of the YAP oncoprotein. Conversely, the restoration of LATS2 expression abrogates the tumor-promoting effects of forced miR-302/367 cluster expression. Collectively, the potent pluripotency regulator-triggered miR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes castration resistance. Thus, targeting this signaling axis may represent a promising therapeutic strategy for CRPC. SN - 1476-5594 UR - https://www.unboundmedicine.com/medline/citation/28745315/miR_302/367/LATS2/YAP_pathway_is_essential_for_prostate_tumor_propagating_cells_and_promotes_the_development_of_castration_resistance_ L2 - http://dx.doi.org/10.1038/onc.2017.240 DB - PRIME DP - Unbound Medicine ER -