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Objective:MicroRNAs(miRNAs)are small non-coding RNAs that are involved in different biological processes by suppressing target gene expression.Altered expression of miR-30a has been reported in non-small cell lung cancer(NSCLC).The aim of the present study was to explore the potential biological role of miR-30a in NSCLC cell proliferation.Methods:MiR-30a was overexpressed via a lentiviral vector system in A549 cell line.The effect of miR-30a on cell proliferation was determined by both in vitro including MTT assay,colony formation and cell cycle analysis and in vivo assays.Luciferase reporter assays and Western blot were performed to identify target association between miR-30a and MAP4K4.Results:Overexpression of miR-30a suppressed A549 cell proliferation by inducing G1 arrest in vitro and in vivo,whereas knockdown of miR-30a dramatically promoted cell proliferation.Bioinformatics analysis and luciferase reporter assay revealed that miR-30a directly targeted 3UTR of MAP4K4 mRNA.Overexpression or knockdown of miR-30a altered both the mRNA and protein levels of MAP4K4.Similar to the inhibitory effects induced by overexpression of miR-30a,shRNA knockdown of MAP4K4 inhibited cell proliferation and caused a cell cycle arrest at the G1 phase.Furthermore,we found that miR-30a could modulate the cell cycle via regulating the expression of MAP4K4 downstream effectors p-ERK1/2,cyclinD1,CDK6 and p27.Conclusions:Our data demonstrates,for the first time,that miR-30a suppresses NSCLC cell proliferation and tumorigenesis by partial direct targeting of the MAP4K4 pathway.Thus,restoration of miR-30a expression may represent a potential therapeutic strategy for NSCLC.