MicroRNA-21 deficiency suppresses prostate cancer progression through downregulation of the IRS1-SREBP-1 signaling pathway.

Autor: Kanagasabai T; Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 37208, USA., Li G; Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 37208, USA., Shen TH; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA., Gladoun N; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA., Castillo-Martin M; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA., Celada SI; Department of Biological Sciences, Tennessee State University, Nashville, TN, 37209, USA., Xie Y; Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 37208, USA., Brown LK; Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 37208, USA., Mark ZA; Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 37208, USA., Ochieng J; Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 37208, USA., Ballard BR; Department of Pathology, Anatomy and Cell Biology, Meharry Medical College, Nashville, TN, 37208, USA., Cordon-Cardo C; Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, 10032, USA., Adunyah SE; Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 37208, USA., Jin R; Department of Urology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Matusik RJ; Department of Urology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA., Chen Z; Department of Biochemistry, Cancer Biology, Neuroscience and Pharmacology, Meharry Medical College, Nashville, TN, 37208, USA. Electronic address: zchen@mmc.edu.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2022 Jan 28; Vol. 525, pp. 46-54. Date of Electronic Publication: 2021 Oct 02.
DOI: 10.1016/j.canlet.2021.09.041
Abstrakt: Sterol regulatory element-binding protein 1 (SREBP-1), a master transcription factor in lipogenesis and lipid metabolism, is critical for disease progression and associated with poor outcomes in prostate cancer (PCa) patients. However, the mechanism of SREBP-1 regulation in PCa remains elusive. Here, we report that SREBP-1 is transcriptionally regulated by microRNA-21 (miR-21) in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of SREBP-1, fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC) in Pten/Trp53 double-null mouse embryonic fibroblasts (MEFs) and Pten/Trp53 double-null mutant mice. Strikingly, miR-21 loss significantly reduced cell proliferation and suppressed the prostate tumorigenesis of Pten/Trp53 mutant mice. Mechanistically, miR-21 inactivation decreased the levels of SREBP-1, FASN, and ACC in human PCa cells through downregulation of insulin receptor substrate 1 (IRS1)-mediated transcription and induction of cellular senescence. Conversely, miR-21 overexpression increased cell proliferation and migration; as well as the levels of IRS1, SREBP-1, FASN, and ACC in human PCa cells. Our findings reveal that miR-21 promotes PCa progression by activating the IRS1/SREBP-1 axis, and targeting miR-21/SREBP-1 signaling pathway can be a novel strategy for controlling PCa malignancy.
(Copyright © 2021. Published by Elsevier B.V.)
Databáze: MEDLINE
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