Investigating microRNA Profiles in Prostate Cancer Bone Metastases and Functional Effects of microRNA-23c and microRNA-4328

Author:

Järemo Helena1ORCID,Semenas Julius1ORCID,Bergström Sofia Halin1,Lundholm Marie1ORCID,Thysell Elin1,Widmark Anders2ORCID,Crnalic Sead3ORCID,Ylitalo Erik Bovinder2,Bergh Anders1ORCID,Brattsand Maria1ORCID,Wikström Pernilla1ORCID

Affiliation:

1. Department of Medical Biosciences, Pathology, Umeå University, 901 87 Umeå, Sweden

2. Department of Radiation Sciences, Oncology, Umeå University, 901 87 Umeå, Sweden

3. Department of Surgical and Perioperative Sciences, Orthopedics, Umeå University, 901 87 Umeå, Sweden

Abstract

MicroRNAs (miRNAs) are aberrantly expressed in prostate cancer (PC), but comprehensive knowledge about their levels and function in metastatic PC is lacking. Here, we explored the differential expression of miRNA profiles during PC progression to bone metastasis, and further focused on the downregulation of miRNA-23c and -4328 and their impact on PC growth in experimental models. Using microarray screening, the levels of 1510 miRNAs were compared between bone metastases (n = 14), localized PC (n = 7) and benign prostate tissue (n = 7). Differentially expressed miRNAs (n = 4 increased and n = 75 decreased, p < 0.05) were identified, of which miRNA-1, -23c, -143-3p, -143-5p, -145-3p, -205-5p, -221-3p, -222-3p and -4328 showed consistent downregulation during disease progression (benign > localized PC > bone metastases). The downregulation of miRNA-23c and -4328 was confirmed by reverse transcription and quantitative polymerase chain reaction analysis of 67 metastasis, 12 localized PC and 12 benign prostate tissue samples. The stable overexpression of miRNA-23c and -4328 in the 22Rv1 and PC-3 cell lines resulted in reduced PC cell growth in vitro, and in the secretion of high levels of miRNA-23c (but not -4328) in extracellular vesicles. However, no tumor suppressive effects were observed from miRNA-23c overexpression in PC-3 cells subcutaneously grown in mice. In conclusion, bone metastases display a profound reduction of miRNA levels compared to localized PC and benign disease. The downregulation of those miRNAs, including miRNA-23c and -4328, may lead to a loss of tumor suppressive effects and provide biomarker and therapeutic possibilities that deserve to be further explored.

Funder

Swedish Research Council

Swedish Cancer Society

Swedish Foundation for Strategic Research

Cancer Research Foundation in Northern Sweden

Prostatacancerförbundet

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference59 articles.

1. Prostate cancer;Rebello;Nat. Rev. Dis. Prim.,2021

2. Androgen pathway resistance in prostate cancer and therapeutic implications;Maughan;Expert Opin. Pharmacother.,2015

3. Treatment Landscape for Patients with Castration-Resistant Prostate Cancer: Patient Selection and Unmet Clinical Needs;Turco;Res. Rep. Urol.,2022

4. MicroRNAs: Small RNAs with a big role in gene regulation;He;Nat. Rev. Genet.,2004

5. MicroRNA signatures in human cancers;Calin;Nat. Rev. Cancer,2006

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