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

Abstract

Abstract. 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 downregulation 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 specific miRNA molecules in lung cancer and ultimately prove to be helpful in the development of prognostic and therapeutic strategies against lung cancer.

Targeted Expression of miR-7 Operated by TTF-1 Promoter Inhibited the Growth of Human Lung Cancer through the NDUFA4 Pathway

“…As shown in Figure 1D, the proliferation of human lung cancer cell line 95D cells decreased significantly in the p-T-miR-7-transfected group (p < 0.05). Moreover, the colon-formation ability of cells was also impaired unmistakably (Figure 1E; p < 0.05), which was consistent with our previous works 17, 18. To confirm this finding, we also detected the expression of cell-growth-related factors such as CDK2, CDK3, CDK4, and CDK6 in lung cancer cells.…”

“…Consistently, our previous work also showed that overexpression of miR-7 could reduce the growth and metastasis of human lung cancer cells in vivo and in vitro 17 . Moreover, the reduced expression of miR-7 was associated with the sites mutation of its promoter region in lung cancer tissues, indicating that miR-7, an important tumor suppressor, could be used as candidate for targeted gene therapy against lung cancer 18, 19…”

“…Moreover, our previous research works also showed that overexpression of miR-7 could inhibit the growth of human lung cancer cells 17, 18. Therefore, we further investigated whether expression of miR-7 operated by TTF-1 promoter could affect the growth of human lung cancer cells in vitro.…”

“…documented that miR-7 could inhibit the growth of human lung cancer cells in vivo. And our recent work reported that the site mutation of miR-7 promoter region contributed to its altered expression in clinical lung cancer tissue 18 . Interestingly, some research works showed that in situ local injection of miR-7 overexpression plasmids could regulate the growth and metastatic potential of human lung cancer cells in vivo via the Akt pathway 43, 44.…”

MicroRNA-7 inhibits cell proliferation, migration and invasion in human non-small cell lung cancer cells by targeting FAK through ERK/MAPK signaling pathway

“…It has been reported that downexpression of miR-7 in NSCLC may be implicated in promoting cancer cell progress, and consequently results in NSCLC growth [19, 24], which were in line with our study results. In addition, miR-7 is a tissue-specific miR to be directly involved in NSCLC [25].…”