ABSTRACT
MYCT1 is an important gene known to regulate cell viability and apoptosis of laryngeal cancer cells. However, the underlying molecular mechanism remains unclear. Here, we show that MAX enhances the expression of miR-181a by directly binding to its promoter, whereas miR-181a targets NPM1 and suppresses its expression in laryngeal cancer cells. MYCT1 and miR-181a decrease cell viability and colony formation through enhanced apoptosis, whereas NPM1 displays opposite effects in laryngeal cancer cells. Their opposing functions are further supported by the findings (a) that miR-181a is down-regulated, while NPM1 is up-regulated in laryngeal cancer, and (b) that either inhibition of miR-181a or overexpression of NPM1 can revert the pro-apoptotic effects of MYCT1 on laryngeal cancer cells through extracellular and intracellular apoptotic pathways. Our data suggest that MYCT1 may synergistically interact with MAX as a co-transcription factor or a component of MAX transcriptional complex, to transcriptionally regulate the expression of miR-181a, which, in turn, decreases NPM1 expression at post-transcriptional levels, leading to enhanced apoptosis in laryngeal cancer cells. These factors may serve as potential targets for early diagnosis and treatment of laryngeal cancer.
