2. Academic Validation
  3. A trio of tumor suppressor miRNA downregulates CREB5 dependent transcription to modulate neoadjuvant hormonal therapy sensitivity

A trio of tumor suppressor miRNA downregulates CREB5 dependent transcription to modulate neoadjuvant hormonal therapy sensitivity

  • Neoplasia. 2023 Jan 3;36:100875. doi: 10.1016/j.neo.2022.100875.
Xueli Wang 1,  Bo Han 2,  Baokai Dou 3,  Lin Gao 4,  Feifei Sun 4,  Mei Qi 5,  Jing Zhang 6,  Jing Hu 7
Affiliations

Affiliations

  • 1 Department of Pathology, Binzhou City Central Hospital, Binzhou 251700, China; The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 2 The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China; Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 3 Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
  • 4 The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 5 Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
  • 6 Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China. Electronic address: [email protected].
  • 7 Department of Pathology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China. Electronic address: [email protected].
PMID: 36603462 DOI: 10.1016/j.neo.2022.100875
Abstract

Neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy (RP) is an approach that can potentially maximize survival outcomes in prostate Cancer (PCa) patients with high-risk disease. Unfortunately, subsets of patients do not respond well to such hormonal therapy. We previously identified several pathological parameters in predicting differences in response to NHT of PCa. However, little is known about the potential role and mechanism of miRNAs mediated NHT resistance (NHT-R) in PCa. Here we demonstrate that miR-l42-3p, miR-150-5p and miR-342-3p are the top downregulated miRNAs in PCa tissues with NHT-R. Functional analysis reveals that the three miRNAs inhibit cell proliferation in vitro. Transfection of miRNAs mimics strengthens the inhibitory effects of bicalutamide and enzalutamide to PCa cells. Luciferase reporter assay reveals that CREB5 is the common target of these three miRNAs. Clinically, high expression level of CREB5 correlates with high Gleason score, advanced tumor stage and NHT-R in PCa tissues. CREB5 expression promotes antiandrogen therapy resistance in LNCaP cells and IL6 signaling pathway may be involved in this process. In all, our findings highlight an important role of miR-142-3p, miR-150-5p, and miR-342-3p in contributing NHT-R by targeting CREB5 in PCa.

Keywords

Bicalutamide; CREB5; Neoadjuvant hormonal therapy; Prostate cancer; miRNA.

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