Let-7a elevates p21(WAF1) levels by targeting of NIRF and suppresses the growth of A549 lung cancer cells.

Down-regulation of let-7 microRNA (miRNA) is a key event in lung cancer. Despite recent advances in survival signaling, the roles of let-7 in the context of lung cancer are not fully clear. In this study, we showed that let-7a, a member of let-7 family, negatively regulated the expression of NIRF through NIRF 3' UTR. We also showed that NIRF was required for the let-7a-mediated elevation of p21(WAF1). These findings suggest that growth-inhibitory effect of let-7a on the A549 cells in vitro and in vivo may be explained in part by le-7a-induced suppression of NIRF and elevation of p21(WAF1). This work reveals a novel regulatory mechanism for let-7a in the control of cellular proliferation and lung carcinogenesis.