Expression of miR-34b in NSCLC and its function in HGF-Met signal pathway / 中华胸心血管外科杂志

ABSTRACT

Objective Background:MicroRNAs (miRNAs) are naturally occurring small non-coding RNAs,play important roles in cancer initiation and progression.Decreases in miRNAs levels are observed in human cancers,indicating that miRNAs may function intrinsically in tumor suppression.However,the underline mechanisms of miRNA function are little known.Methods MiR-34b in non-small cell lung cancer (NSCLC) tissues was detected using quantitative Real-Time PCR.The relations between miR-34b expression level and clinical pathological parameters were assessed.For in vitro studies,lung cancer cells were transfected with double stranded synthetic miRNA mimics and scrambled controls.Immunohistochemistry technology was explored to validate the related downstream proteins of miR-34b.Results Expression of miR-34b was lower in NSCLC tissues than that in pericarcinous tissues of lung cancer.Additionally,the Spearman correlation test showed lower miR-34b expression was correlated with higher lymph node metastasis (P =0.031).In vitro gain-of-function experiments indicated that miR-34b suppressed cell proliferation by inducing cell apoptosis.IHC results showed relations between lower miR-34b and over-expression of phospho-Met (P =0.012).Conclusion MiR-34b down-regulates Met,following with subsequent changes of downstream p53 and Mdm2,and inversely p53 up-regulates miR-34b in a feedback loop.MiR-34b plays profound roles in progression of NSCLC by inducing apoptosis and decreasing lymph node metastasis.