miR-34a inhibits tumorigenesis of NSCLC via targeting SIRT6.

: Non-small cell lung cancer (NSCLC) remains the leading cause of deaths around the world. Therefore, improving the diagnostic and treatments of NSCLC are urgently needed. The microRNA-34a (miR-34a) and SIRT6 are associated with NSCLC. miR-34a is downregulated in three NSCLC cells lines (A549, H460, and H1299). The functions of SIRT6 in NSCLC are controversial. Some reports have shown that SIRT6 is downregulated in NSCLC cells, while other reports have shown that SIRT6 is upregulated in NSCLC tissues as well as SIRT6 overexpression is associated with the poor prognosis of NSCLC. SIRT6 is a direct target of miR-34a in human keratinocytes (HKCs). However, the relationship between SIRT6 and miR-34a in NSCLC has not been investigated. In this study, we found that the SIRT6 was upregulated in NSCLC tissues while miR-34a was downregulated in NSCLC tissues compared with those in their normal counterparts. Overexpression of miR34a or downregulation of SIRT6 promoted A549 cells apoptosis, cell cycle arrest in vitro and further inhibited the tumor formation in vivo. SIRT6 was indeed the target gene of miR-34a, which was proved by the luciferase reporter data. Therefore, we conclude that SIRT6 was the target gene of miR-34a in NSCLC. miR-34a acted as a cancer suppressor in NSCLC via targeting the SIRT6.