MiRNA-145 inhibits non-small cell lung cancer cell proliferation by targeting c-Myc

Micrornas are important gene regulators that potentially play a profound role in tumorigenesis. increasing evidence indicates that mir-145 is a tumor suppressor capable of inhibiting breast and colon cancer cell growth both in vitro and in vivo. however,the biological function of mir-145 in non-small cell lung cancer (nsclc) is largely unknown. in colon cancer cells,c-myc is a confirmed direct target for mir-145. the aim of this work was to investigate the effect of mir-145 and c-myc on proliferation of nsclc cells,using the nsclc cell lines a549 and h23 as models. we determined the expression level of mir-145 in tumor tissues relative to adjacent non-tumor tissues,and in nsclc cell lines relative to non-malignant lung cells. downregulation of mir-145 was seen in tumor tissues and the two nsclc cell lines by real-time quantitative reverse transcription polymerase chain reaction. mtt and focus formation assays were conducted to measure cell proliferation rates. cell growth was inhibited and the g1/s transition was blocked by mir-145 in transfection assays of a549 and h23 cells. we further showed that c-myc was a direct target for mir-145. introduction of mir-145 dramatically suppressed the c-myc/eif4e pathway,which was demonstrated to be crucial for cell proliferation in nsclc cells. furthermore,we found that cdk4 was regulated by mir-145 in cell cycle control. taken together,our study results demonstrate that mir-145 inhibits proliferation of nsclc cells through c-myc. increasing mir-145 expression may provide a novel approach for the treatment of nsclc. © 2010 chen et al; licensee biomed central ltd.