Inhibition of MiR-199a-5p Reduced Cell Proliferation in Autosomal Dominant Polycystic Kidney Disease through Targeting CDKN1C
Lijun Sun, Jiaqi Zhu, Ming Wu, Haipeng Sun, Chenchen Zhou, Lili Fu, Chenggang Xu, Changlin Mei
Division of Nephrology, Nephrology Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China (mainland)
Med Sci Monit 2015; 21:195-200
With a prevalence of about 1:500 to 1:1,000, autosomal dominant polycystic kidney disease (ADPKD) often causes renal failure, with many serious complications. However, there is no Food and Drug Administration (FDA) approved therapy available.
Material and Methods: MiR-199a-5p level in ADPKD patient samples, rat model, and cell lines were determined with Realtime PCR assay. After miR-199a-5p inhibitor was transfected, we detected the cell proliferation and apoptosis using an MTT assay and an Annexin V-FITC staining kit, respectively. Finally, TargetScan version 5.1 was used to predict the miRNA target and the target gene of miR-199a-5p was proved by a Luciferase assay.
Results: We identified a dramatically up-regulated microRNA, miR-199a-5p, in ADPKD tissues and cell lines. Our data show that inhibition of miR-199a-5p suppressed cyst cells proliferation and induced cell apoptosis. We found that miR-199a-5p might exert this effect through targeting CDKN1C/p57.
Conclusions: Up-regulation of miR-199a-5p in ADPKD tissues might promote cell proliferation through suppressing CDKN1C, suggesting miR-199a-5p as a novel target for ADPKD treatment.
Keywords: Cell Line, Animals, Cell Movement - genetics, Cyclin-Dependent Kinase Inhibitor p57 - metabolism, Disease Models, Animal, Heterozygote, Kidney - metabolism, MicroRNAs - metabolism, Polycystic Kidney, Autosomal Dominant - metabolism, Rats, Up-Regulation