MicroRNA-363-3p promotes apoptosis in response to cadmium-induced renal injury by down-regulating phosphoinositide 3-kinase expression

作者：Chen, Jiabin; Lai, Weina; Deng, Yaotang; Liu, Min; Dong, Ming; Liu, Zhidong; Wang, Ting; Li, Xiang; Zhao, Zhiqiang; Yin, Xiao; Yang, Jinmei; Yu, Rian; Liu, Lili^*

来源：Toxicology Letters, 2021, 345: 12-23.

DOI：10.1016/j.toxlet.2021.04.002

• Cadmium
• Kidney
• Apoptosis
• MicroRNA-363-3p
• Phosphoinositide 3-kinase

We previously determined that specific microRNAs (miRNAs) are involved in renal pathophysiological occurrences induced by cadmium (Cd) in rats. This study expands our studies on miRNAs, determining their role in Cd-induced nephrotoxicity in occupational workers. We performed miRNA microarray analyses of blood and urine samples from patients diagnosed as occupational chronic Cd poisoning (OCCP) with abnormally elevated concentrations of urinary beta-2-microglobulin (U-beta(2)-MG), an indicator of tubular proteinuria. We also performed in vitro bioinformatics-based investigations of apoptosis-related genes targeted by miRNAs involved in the biological response to Cd exposure. We tested five differentially expressed miRNAs and determined a significant increase of sera miR-363-3p. Also, we determined that miR-363-3p increase is associated with phosphoinositide 3-kinase (PI3K) down-regulation and the suppressed proliferation and enhanced apoptosis of renal tubule epithelial cells. The obtained results suggest miR-363-3p involvement in the pathophysiology of Cd-induced renal injury in humans and maybe considered for possible interventional therapeutic strategies for Cd-associated kidney damage.

• 单位
  广东省人民医院; 广东药学院; 广州医学院; 南方医科大学