MicroRNA-34a Suppresses Non-small-cell Lung Cancer Via Epidermal Growth Factor Receptor

Lung cancer,is the leading cause of tumor death,and the mortality rate is still higher for decades.Based on histology,lung cancer is mainly divided into small cell lung cancer(SCLC,about 20%)and non small cell lung cancer(NSCLC,about 80%).NSCLC five years survival rate is below 15%.EGFR(epidermal growth factor receptor)has been identifed as an oncogenic driver of NSCLC,especially activated mutations EGFR and its inhibition with specifc TKIs can generate dramatic tumor responses.Studies have shown that EGFR plays signifcant roles in the progression of NSCLC,and most of the NSCLCs have EGFR mutations.MiRNAs are small non-coding RNAs consisting of 20–23 nucleotides(nt).MiRNAs play an important regulatory role in a variety of physiological and pathological processes,especially in oncogenesis.MiR-34 a is an important antitumor gene in many cancers,but its role is still unclear in lung cancer.Our results demonstrated that miR-34 a was downregulated in NSCLC patient samples and NSCLC cell lines,over-expression miR-34 a can inhibit cell proliferation,promote apoptosis,and arrest cell-cycle progression.Through luciferase activity of the report gene and western blot,we found that miR-34 a can directly target EGFR,binding with its 3’UTR,promote apoptosis and arrest cell-cycle in G1 phase to S phase.Furthermore,in vivo experiments demonstrated that miR-34 a suppressed tumor growth,both in the A549 xenograft model,as well as in metastatic tumors in nude mice.In summary,our study demonstrated that miR-34 a can inhibit the proliferation,cycle progression and promote apoptosis of NSCLC by targeting EGFR.It is expected that miR-34 a will become drug target and prognosis marker,and also provide new ideas for precision medicine for NSCLC.