title: Inhibiting microRNA-449 Attenuates Cisplatin-Induced Injury in NRK-52E Cells Possibly via Regulating the SIRT1/P53/BAX Pathway.
abstract: BACKGROUND
  Acute kidney injury (AKI) is quite common in the patients who frequently use the anticancer drug cisplatin. microRNAs (miRNAs) are powerful tools in modulating the expression of key factors in disease progression, but little is known about roles of miRNAs in AKI. This study explored the expression and function of miR-449 in cisplatin-induced AKI.
  
  
  METHODS
  Rat renal proximal tubular cell line NRK-52E was used for cisplatin treatment and miR-449 sponge transfection. MTT assay and flow cytometry were performed to detect cell viability and apoptosis in different cell groups. Protein expression of sirtuin 1 (SIRT1), acetylated p53, and BCL-associated X protein (BAX) was detected to deduce the possible regulatory mechanism of miR-449.
  
  
  RESULTS
  Results showed that cisplatin treatment in NRK-52E cells significantly up-regulated miR-449 levels (P<0.05), inhibited cell viability (P<0.05), accelerated cell apoptosis (P<0.05), and changed SIRT1, acetylated p53, and BAX protein levels (P<0.01). However, inhibiting miR-449 by its sponge transfection in cisplatin-treated cells significantly promoted cell viability (P<0.05), suppressed cell apoptosis (P<0.05), elevated SIRT1 expression (P<0.01), and inhibited acetylated p53 and BAX protein levels (P<0.001).
  
  
  CONCLUSIONS
  These results indicate that inhibiting miR-449 allows the attenuation of cisplatin-induced injury in NRK-52E cells, suggesting that miR-449 is a potential target for treating AKI. miR-449 regulates the SIRT1/p53/BAX pathway, which may be its possible mechanism in modulating cell apoptosis of cisplatin-induced AKI. Further verification and a thorough understanding are necessary for targeting miR-449 in AKI treatment.
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).
authors.forename: Wen
authors.initials: W
authors.lastname: Qin
authors.affiliation: Department of Reproductive Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.affiliation: Department of Geriatric Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Endocrinology and Metabolism, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (mainland).
authors.forename: Ning
authors.initials: N
authors.lastname: Xia
authors.affiliation: , Guangxi Medical University, Nanning, Guangxi, China (mainland).
authors.forename: Kunling
authors.initials: K
authors.lastname: Yang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D035683:MicroRNAs / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C588007:MIRN449 microRNA, rat; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D056564:Sirtuin 1; D002945:Cisplatin