Identification of microRNA signature and potential pathway targets in prostate cancer.

Prostate cancer (PC) is the most common and the second leading cause of cancer-related death among American men. Early diagnosis is a prerequisite to improving therapeutic benefits. However, the current clinical biomarkers for PC do not reliably decipher indolent PC from other urogenital disorders. Thus, effective clinical intervention necessitates development of new biomarkers for early detection of PC. The present study aimed to identify the miRNA signature in organ-confined (Gleason Score 6) prostate tumors. MicroRNA (miRNA/miR) array analysis identified 118 upregulated and 73 downregulated miRNAs in microdissected tumors in comparison to matched neighboring normal prostate epithelium. The miRs-Plus-A1083, -92b-5p, -18a-3p, -19a-3p, -639, -3622b-3p, -3189-3p, -155-3p, -410, -1179, 548b-5p, and -4469 are predominantly expressed (7-11-fold), whereas miRs-595, 4490, -3120-5p, -1299, -21-5p, -3677-3, -let-7b-5p, -5189, 3-121-5p, -4518, -200a-5p, -3682-5p, -3689d, -3149 represent the most downregulated (12-113-fold) miRNAs in microdissected prostate tumors. The array expression profile of selected miRNA signature and their potential mRNA targets was validated by qRT-PCR analysis in PC cell lines. Integrated in silico and computational prediction analyses demonstrated that the dysregulated miRNA signature map to key regulatory factors involved in tumorigenesis, including cell cycle, apoptosis, and p53 pathways. The newly identified miRNA signature has potential clinical utility as biomarkers, prognostic indicators, and therapeutic targets for early detection of PC. Further studies are needed to assess the functional significance and clinical usefulness of the identified miRNAs.

Experimental biology and medicine (Maywood, N.J.). 2016 Jan 29 [Epub ahead of print]

Ahmed A Moustafa, Mohammed Ziada, Abubaker Elshaikh, Amrita Datta, Hogyoung Kim, Krzysztof Moroz, Sudesh Srivastav, Raju Thomas, Jonathan L Silberstein, Krishnarao Moparty, Fatma Elzahraa H Salem, Ola H El-Habit, Asim B Abdel-Mageed

Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Department of Pathology, Tulane University School of Medicine, New Orleans, LA 70112, USA., Department of Biostatistics, Tulane University School of Tropical Medicine, New Orleans, LA 70112, USA., Zoology and Entomology Department, Faculty of Science, Helwan University, Cairo 11790, Egypt., Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA .