Promoter mutation of tumor suppressor microRNA-7 is associated with poor prognosis of lung cancer.

The significance of promoter mutations of microRNAs (miRNAs) in lung cancer is poorly understood. Recent evidence demonstrated that miRNA-7 (miR-7), a unique member of the miRNA family, exhibited decreased expression and has emerged as an important regulator in lung tumorigenesis. However, the mechanism underlying the down-regulation of miR-7 in lung cancer remains largely unknown. In this study, we investigated the sites of mutation of the miR-7 promoter in lung cancer tissues using DNA sequencing. We identified a G^C change at the -617 site (25/39, 64.1%) and an A-^G change at the -604 site (20/39, 51.3%) in the miR-7 promoter region in lung cancer tissues. Moreover, the expression of miR-7 in cancer tissue with promoter site mutations was lower compared with that in cancer tissue without mutations (P<0.05). Furthermore, we demonstrated that mutations at these sites may decrease the activity of the miR-7 promoter and alter the expression of miR-7. Notably, mutations at these sites of the miR-7 promoter were found to be closely associated with poor prognosis of lung cancer patients (P=0.037). These data may provide novel insight on the altered expression of speciic miRNA molecules in lung cancer and ultimately prove to be helpful in the development of prognostic and thera- peutic strategies against lung cancer. [ABSTRACT FROM AUTHOR]