MiR-136 Suppresses the Aggressive Proliferation of Non-Small Cell Lung Cancer Through Restraining Histone Deacetylase 1 (HDAC1) and Phosphorylation of the Janus Kinase 2/Signal Transducer and Activator of Transcription 3 (Jak2/STAT3) Pathway

Abstract

microRNA-136 can inhibit the proliferating activity of malignant cells and also participate in chemotherapy resistance of colorectal cancer via modulating HDAC1. This study assessed miR-136’s effect on NSCLC cell proliferation and underlying mechanisms. Tumor tissues and paracancerous tissues from NSCLC patients were collected to measure miR-136 and HDAC1 level. Cells were transfected with miR-136-mimics, miR-136-inhibitors or miR-136 mimics+HDAC1-OE followed by analysis of cell viability and apoptosis by CCK-8 method and flow cytometry, phosphorylation of Jak2/STAT3 by western blot. miR-136 was significantly downregulated in tumor tissues and NSCLC cells, accompanied by upregulated HDAC1. miR-136 overexpression suppressed HDAC1 expression, retarded phosphorylation and activation of Jak2/STAT3 signaling, reduced NSCLC cell viability and enhanced apoptosis. In addition, co-transfection of miR-136-mimics and HDAC1-OE reversed the inhibitory effects of miR-136 on NSCLC cells. In conclusion, miR-136 is reduced and HDAC1 is increased in NSCLC and miR-136 overexpression inhibited NSCLC cell proliferation and increased apoptosis possibly through regulating HDAC1/Jak2/STAT3 signal pathway, indicating that miR-136 might be a novel target for the treatment of NSCLC.