MiR-326 regulates cell proliferation and migration in lung cancer by targeting phox2a and is regulated by HOTAIR.

Recent findings indicate that microRNAs (miRNAs) play a crucial role in lung cancer development, progression and regression. In our previous study, we identified miR-326 is down-regulated in lung cancer. However, the role of miR-326 hasn't been revealed yet. The aim of the current study is to investigate the function and regulation mechanism of miR-326 in lung cancer. MTT assays, Transwell migration assays and xenograft model in nude mice were carried to detect the effects of miR-326 on cell proliferation, migration and tumor growth in nude mice. Flow cytometry was used to analyze the effects of miR-326 on cell cycle and apoptosis. By using siRNAs and luciferase assays, we also demonstrated that Phox2a is a functional target of miR-326, and that miR-326 is regulated by long non-coding RNA HOTAIR through silencing HOTAIR. Enforced expression of miR-326 inhibited cell proliferation and migration in vitro and tumor growth in nude mice, decreased proportion of cells in S phase and increased cell apoptosis in both A549 and H838 cells. In addition, we found miR-326 bound to 3'UTR of Phox2a but not KLF3, and enforced expression of miR-326 decreased accumulation of Phox2a in both A549 and H838. Moreover, exogenous expression of Phox2a compromised inhibitory effects of miR-326 on cell proliferation and migration. We also found silencing of HOTAIR caused increased expression of miR-326. miR-326 regulates cell proliferation and migration in lung cancer by targeting Phox2a and is regulated by HOTAIR.