Sun Lijun, Zhu Jiaqi, Wu Ming, Sun Haipeng, Zhou Chenchen, Fu Lili, Xu Chenggang, Mei Changlin
Division of Nephrology, Nephrology Institute of CPLA, Changzheng Hospital, Second Military Medical University, Shanghai, China (mainland).
Med Sci Monit. 2015 Jan 15;21:195-200. doi: 10.12659/MSM.892141.
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/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.
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.
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.
常染色体显性多囊肾病(ADPKD)的患病率约为1:500至1:1000,常导致肾衰竭,并伴有许多严重并发症。然而,目前尚无美国食品药品监督管理局(FDA)批准的治疗方法。
材料/方法:采用实时定量PCR检测ADPKD患者样本、大鼠模型和细胞系中miR-199a-5p的水平。转染miR-199a-5p抑制剂后,分别使用MTT法和Annexin V-FITC染色试剂盒检测细胞增殖和凋亡情况。最后,使用TargetScan 5.1版本预测miRNA靶点,并通过荧光素酶报告基因检测法验证miR-199a-5p的靶基因。
我们在ADPKD组织和细胞系中鉴定出一种显著上调的微小RNA,即miR-199a-5p。我们的数据表明,抑制miR-199a-5p可抑制囊肿细胞增殖并诱导细胞凋亡。我们发现miR-199a-5p可能通过靶向CDKN1C/p57发挥这种作用。
ADPKD组织中miR-199a-5p的上调可能通过抑制CDKN1C促进细胞增殖,提示miR-199a-5p可作为ADPKD治疗的新靶点。