Research Papers:
miR-33a is a tumor suppressor microRNA that is decreased in prostate cancer
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Abstract
Omer Faruk Karatas1,2, Jianghua Wang1, Longjiang Shao1, Mustafa Ozen3, Yiqun Zhang4, Chad J. Creighton4,5 and Michael Ittmann1
1Department of Pathology and Immunology and Michael E. DeBakey Department of Veterans Affairs Medical Center, Houston, TX, USA
2Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum, Turkey
3Department of Medical Genetics, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey
4Dan L. Duncan Cancer Center Division of Biostatistics, Houston, TX, USA
5Department of Medicine, Baylor College of Medicine, Houston, TX, USA
Correspondence to:
Michael Ittmann, email: [email protected]
Keywords: prostate cancer, miR-33a, PIM1, SREBF2, CPT1A
Abbreviations: PCa: prostate cancer; UTR: untranslated region
Received: May 27, 2017 Accepted: July 12, 2017 Published: July 24, 2017
ABSTRACT
Prostate cancer is one of the most frequently diagnosed neoplasms among men worldwide. MicroRNAs (miRNAs) are involved in numerous important cellular processes including proliferation, differentiation and apoptosis. They have been found to be aberrantly expressed in many types of human cancers. They can act as either tumor suppressors or oncogenes, and changes in their levels are associated with tumor initiation, progression and metastasis. miR-33a is an intronic miRNA embedded within SREBF2 that has been reported to have tumor suppressive properties in some cancers but has not been examined in prostate cancer. SREBF2 increases cholesterol and lipid levels both directly and via miR-33a action. The levels of SREBF2 and miR-33a are correlated in normal tissues by co-transcription from the same gene locus. Paradoxically, SREBF2 has been reported to be increased in prostate cancer, which would be predicted to increase miR-33a levels potentially leading to tumor suppression. We show here that miR-33a has tumor suppressive activities and is decreased in prostate cancer. The decreased miR-33a increases mRNA for the PIM1 oncogene and multiple genes in the lipid β-oxidation pathway. Levels of miR-33a are not correlated with SREBF2 levels, implying posttranscriptional regulation of its expression in prostate cancer.
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