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15 January 2015 : Original article

Inhibition of MiR-199a-5p Reduced Cell Proliferation in Autosomal Dominant Polycystic Kidney Disease through Targeting CDKN1C

Lijun SunABE, Jiaqi ZhuABC, Ming WuBCD, Haipeng SunBCD, Chenchen ZhouBDF, Lili FuBDF, Chenggang XuCDE, Changlin MeiADEG

DOI: 10.12659/MSM.892141

Med Sci Monit 2015; 21:195-200

Abstract

BACKGROUND: 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, Cyclin-Dependent Kinase Inhibitor p57 - metabolism, Disease Models, Animal, Heterozygote, Kidney - metabolism, Polycystic Kidney, Autosomal Dominant - metabolism, Rats

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750