MicroRNA-34a/EGFR axis plays pivotal roles in lung tumorigenesis.

ABSTRACT: MicroRNAs (miRNAs) are vital in the regulation of tumor progression and invasion. Dysregulation of miRNAs has been linked to the development of various types of human cancers, including non-small-cell lung cancer (NSCLC). However, the effect of miRNA-34a (miR-34a), a key regulator of tumor suppression, on the tumorigenesis of NSCLC has not been fully elaborated. Herein, we reveal that miR-34a is significantly downregulated in NSCLC tissues and cell lines, suggesting that miR-34a might function as a tumor suppressor in lung cancer. We also confirmed that epidermal growth factor receptor (EGFR) is a direct target of miR-34a, and our data reveal that siRNA knockdown of EGFR can inhibit cell proliferation, promote apoptosis and arrest cell-cycle progression. In addition, EGFR can reverse the suppressive function of miR-34a overexpression on proliferation and cell apoptosis. Furthermore, in vivo experiments demonstrated that miR-34a suppress tumor growth, both in the A549 xenograft model, as well as in the metastatic tumors in nude mice. Taken together, our findings suggest that miR-34a inhibits NSCLC tumor growth and metastasis through targeting EGFR.

SUBMITTER: Li YL 

PROVIDER: S-EPMC5608916 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature