Small extracellular vesicle-associated miR-6068 promotes aggressive phenotypes of prostate cancer through miR-6068/HIC2/SIRT1 axis.

Autor:	Gaballah MSA; Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University College Station 77843, USA.; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University Helwan, Cairo 11795, Egypt., Ali HEA; Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University College Station 77843, USA., Hassan ZA; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University Helwan, Cairo 11795, Egypt., Mahgoub S; Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University Helwan, Cairo 11795, Egypt., Ali HI; Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University College Station 77843, USA., Rhim JS; Department of Surgery, Uniformed Services University of The Health Sciences Bethesda, MD 20814, USA., Zerfaoui M; Department of Surgery, Tulane University School of Medicine New Orleans, LA 70112, USA., El Sayed KA; School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe Monroe, LA 71203, USA., Stephen D; Department of Pathology, Edward Via College of Osteopathic Medicine Auburn, LA 36832, USA., Sylvester PW; School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe Monroe, LA 71203, USA., Abd Elmageed ZY; Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University College Station 77843, USA.; Department of Biomedical Sciences, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana at Monroe Monroe, LA 71203, USA.
Jazyk:	angličtina
Zdroj:	American journal of cancer research [Am J Cancer Res] 2022 Aug 15; Vol. 12 (8), pp. 4015-4027. Date of Electronic Publication: 2022 Aug 15 (Print Publication: 2022).
Abstrakt:	Early diagnosis and treatment of patients with aggressive prostate cancer (PCa) remains a clinically unmet need. We aimed to determine the levels of small extracellular vesicle (sEV)-associated microRNAs (miRs); miR-4737, miR-6068, and miR-6076 in a large panel of PCa cells and delineate the biological significance of miR-6068 in promoting PCa cells. sEVs were isolated from the conditioned medium of PCa cells, followed by RNA extraction and quantitative Real-Time PCR analysis. Functional assays were performed, and the protein expression of hypermethylated in cancer 2 (HIC2), as a potential miR-6068 target gene, was evaluated in PCa tissues by immunohistochemistry. sEV-associated miR-6068, miR-4737, and miR-6076 levels displayed large and significant differences compared to normal cells. miR-6068 was explicitly upregulated in sEV of PC-3 and CWR-R1ca cells (P<0.010). Suppression of miR-6068 in CWR-R1ca cells decreased cell proliferation, colony formation, and cell migration. In contrast, upregulation of miR-6068 in RC77T/E cells decreased HIC2 levels and increased cell aggressive phenotypes. The overexpression of HIC2 in PCa tissues was primarily observed in the cytoplasm compared to benign prostatic hyperplasia (BPH) and normal tissues (P<0.0001). This study confirms the differential packaging of miR-4737, miR-6068, and miR-6076 in sEVs of PCa cells. MiR-6068 promotes PCa cells to acquire aggressive phenotypes by inhibiting the HIC2/Sirtuin 1 (SIRT1) axis. Competing Interests: None. (AJCR Copyright © 2022.)
Databáze:	MEDLINE
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