title: miR-101 Enhances Cisplatin-Induced DNA Damage Through Decreasing Nicotinamide Adenine Dinucleotide Phosphate Levels by Directly Repressing Tp53-Induced Glycolysis and Apoptosis Regulator Expression in Prostate Cancer Cells.
abstract: Tp53-induced glycolysis and apoptosis regulator (TIGAR) enhances the pentose phosphate pathway, thereby contributing directly to DNA repair due to generation of nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate, two key precursors of DNA synthesis and repair. Targetscan database showed that miR-101 was predicted to potentially target TIGAR. Therefore, we speculated that miR-101 could enhance cisplatin-induced DNA damage by directly repressing TIGAR expression in prostate cancer cells. We found that upregulation of miR-101 inhibited viability, induced apoptosis, increased glycolysis rate and fructose-2,6-bisphosphate levels, decreased glucose-6-phosphate dehydrogenase expression and NADPH levels, and enhanced cisplatin-induced DNA damage in prostate cancer cells. We also demonstrated that TIGAR was a direct target of miR-101 by using luciferase activity assay. Furthermore, this study revealed that the roles of knockdown of TIGAR were similar to miR-101 upregulation in prostate cancer cells. Taken together, miR-101 inhibited viability, induced apoptosis, reprogramed glucose metabolism, and enhanced cisplatin-induced DNA damage through decreasing NADPH levels by directly suppressing the expression of TIGAR in prostate cancer cells.
authors.affiliation: 1 Department of Urology, Shandong Shanxian Central Hospital , Heze, People's Republic of China .
authors.forename: Shiqiao
authors.initials: S
authors.lastname: Huang
authors.affiliation: 1 Department of Urology, Shandong Shanxian Central Hospital , Heze, People's Republic of China .
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 1 Department of Urology, Shandong Shanxian Central Hospital , Heze, People's Republic of China .
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: 2 Department of Orthopedics, Shandong Shanxian Central Hospital , Heze, People's Republic of China .
authors.forename: Yiyong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 1 Department of Urology, Shandong Shanxian Central Hospital , Heze, People's Republic of China .
authors.forename: Shangren
authors.initials: S
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000633:toxicity; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D009249:NADP; D010744:Phosphoric Monoester Hydrolases; C512708:TIGAR protein, human; D005947:Glucose; D002945:Cisplatin
keywords: NADPH; TIGAR; glycolysis; miR-101; pentose phosphate pathway; prostate cancer