The Mechanism Of MiR-141-3p In Regulating The Senescence Of NIH3T3

To explore the age-associated expression change of miR-141-3p and its related regulatory mechanism for aging process, animal and cellular aging models were constructed. The results from rats by high-throughput deep-sequencing showed that, as compared with the young group, the expression of miR-141-3p was down-regulated significantly in the old, while up-regulated in adults. Further results from qPCR had validated its age-related change in expression. Intriguingly, one of the predicted target genes of mi R-141-3p is Keap1(Kelch-like ECH-associated protein-1) that through regulating the activation of a transcription factor Nrf2(NF-E2-related factor 2) controls oxidative stress. Therefore, the regulating mechanism of miR-141-3p on Keap1 and Nrf2 was investigated with the NIH3T3 aging model constructed by H2O2 treatment. The results illustrated that the senescent cells displayed a lower growth rate, raising positive rate of SA-β-gal staining, decreasing expression of miR-141-3p, and increasing protein levels of Keap1 and Nrf2, in contrast with the control. However, transfected the senescent cells with miR-141-3p mimic could ameliorate the age-related phenotypes and down-regulate both mRNA and protein levels of the Keap1 and the Nrf2. On the contrary, the mi R-141-3p inhibitor could enhance the cellular age-related phenotypes and up-regulate both mRNA and protein levels of the Keap1 and the Nrf2. In conclusion, these findings indicated that the declined expression of miR-141-3p in late age might promote aging process through regulating the Keap1-Nrf2/ARE oxidative stress pathway.