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Article Dans Une Revue Oncogene Année : 2022

Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity

Résumé

Abstract Disease progression and therapeutic resistance of prostate cancer (PC) are linked to multiple molecular events that promote survival and plasticity. We previously showed that heat shock protein 27 (HSP27) acted as a driver of castration-resistant phenotype (CRPC) and developed an oligonucleotides antisense (ASO) against HSP27 with evidence of anti-cancer activity in men with CRPC. Here, we show that the tumor suppressor Menin ( MEN1 ) is highly regulated by HSP27. Menin is overexpressed in high-grade PC and CRPC. High MEN1 mRNA expression is associated with decreased biochemical relapse-free and overall survival. Silencing Menin with ASO technology inhibits CRPC cell proliferation, tumor growth, and restores chemotherapeutic sensitivity. ChIP-seq analysis revealed differential DNA binding sites of Menin in various prostatic cells, suggesting a switch from tumor suppressor to oncogenic functions in CRPC. These data support the evaluation of ASO against Menin for CRPC.

Dates et versions

hal-03599176 , version 1 (06-03-2022)

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Chaïma Cherif, Dang Tan Nguyen, Clément Paris, Thi Khanh Le, Thibaud Sefiane, et al.. Menin inhibition suppresses castration-resistant prostate cancer and enhances chemosensitivity. Oncogene, 2022, 41 (1), pp.125-137. ⟨10.1038/s41388-021-02039-2⟩. ⟨hal-03599176⟩
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