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Updated: Feb 25, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
miR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes the development of
1State 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.
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.
Insights
A potent pluripotency regulator, the miR-302/367 cluster, drives prostate cancer (PCa) growth and castration resistance by targeting LATS2 and activating YAP. Targeting this pathway offers a new strategy for castration-resistant prostate cancer (CRPC).
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Advanced prostate cancer (PCa) often recurs as castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT).
- Prostate cancer stem cells (CSCs) are implicated in PCa progression and recurrence.
- The miR-302/367 microRNA cluster is a known regulator of pluripotency.
Purpose of the Study:
- To investigate the role of the miR-302/367 cluster in prostate cancer progression and castration resistance.
- To elucidate the molecular mechanism by which miR-302/367 influences PCa growth and ADT resistance.
Main Methods:
- Analysis of miR-302/367 cluster expression in prostate tumors.
- In vitro and in vivo experiments involving forced expression or knockdown of the miR-302/367 cluster in PCa cells.
- Investigation of LATS2 as a direct target of miR-302/367.
- Assessment of the Hippo signaling pathway components, LATS2 and YAP, and their role in the observed effects.
Main Results:
- The miR-302/367 cluster is upregulated in prostate tumors.
- Forced miR-302/367 expression enhanced PCa cell growth and castration resistance in vitro and in vivo.
- Knockdown of miR-302/367 suppressed tumor formation, growth rate, and weight.
- miR-302/367 directly targets LATS2, leading to reduced LATS2 expression.
- Downregulation of LATS2 by miR-302/367 promotes YAP activation and contributes to castration resistance.
Conclusions:
- The miR-302/367/LATS2/YAP pathway is crucial for prostate tumor-propagating cells and promotes castration resistance.
- Targeting this signaling axis presents a potential therapeutic strategy for CRPC.
