[Analysis of microRNA regulatory network in cochlear hair cells with oxidative stress injury]

Objective: To analysis the important genes and functions of cochlear hair cells with oxidative stress injury, by the construction of gene regulatory network which based on different miRNA in cochlear hair cells in vitro with oxidative stress injury, and to explore the molecular mechanisms of deafness based on oxidative stress injury. Method: The oxidative stress damage cochlear hair cell model was induced by 200 μmol/L t-BHP exposure in vitro. Small RNA deep sequencing analyzed the difference expression of miRNA and contructed gene regulatory network by 6 most significant difference miRNA. The important interaction genes in regulatory network were screened and important genes function were annotated by GeneCards. Result: There were 24 different miRNAs in cochlear hair cells with oxidative stress injury by sRNA deep sequencing.Six most significant difference miRNA were: mir-1934 (logFC=2.367 947, P=2.35×10^-7), mir-411 (logFC=2.093 687, P=3.13×10^-6), mir-717 (logFC=1.927 67, P=3.24×10^-5), mir-503 (logFC=-2.021 45, P=3.07×10^-6), mir-467e (logFC=-1.953 28, P=0.000 137), and mir-699o (logFC=-1.950 06, P=0.000 517). Eleven important genes in miRNA regulatory network were: Akt1, Src, Ctnnb1, Creb1, Ccnd1, Egfr, Gsk3b, Pten, Cdh1, Fras1, and Ccnd2. Their main functions were to regulate hair cells apoptosis and proliferation by different intracellular signaling pathways. Conclusion: There are many signaling pathways (PI3K-AKT/PKB signaling pathway, AKT/PKB signaling pathway, Wnt signaling pathway, ERK signaling pathway, and Ras signaling pathway) involved in the regulation of apoptosis and proliferation in cochlear hair cells with oxidative stress injury and these signaling pathways are linked to each other to form a network. PI3K-AKT/PKB signaling pathway seems to be the most active in cochlear hair cells with oxidative stress injury.