P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis (PNAS, 2010, 107:6334-6339)

報告日期: 2010/10/15
報告時間: 16:00/16:50
報告學生: 許晉源
講評老師: 吳梨華
附件下載:

Full Text:  http://basicmed.med.ncku.edu.tw/admin/up_img/991015-2.pdf

P53-induced microRNA-107 inhibits HIF-1 and tumor angiogenesis

Yamakuchi M., Lotterman C. D., Bao C., Hruban R. H., Karim B., Mendell J. T., Huso D., Lowenstein C. J.

PNAS. 107, 6334-6339 (2010)

 

Speaker:許晉源

Commentator:吳梨華 老師

Time: 2010/10/15 1600 - 1650

PlaceRoom 602

 

Abstract:

The p53 tumor suppressor protein mediates cell cycle arrest, apoptosis, and suppression of angiogenesis, results from its ability to transcriptionally activate a wide variety of target genes. The role of p53 in the regulation of angiogenesis is less well understood. In this report, the authors demonstrate that microRNA-107 (miR-107) transcriptional level is regulated by p53 under hypoxic signaling. They found that p53 regulates miR-107 which is an expressed microRNA by human colon cancer specimens. miR-107 down-regulates hypoxic signaling by inhibit the expression of hypoxia inducible factor-1β (HIF-1β). In human colon cancer cells, knockdown of endogenous miR-107 increase HIF-1β expression and hypoxic signaling. On the other hand, they used lentiviral vectors (LV-GFP or LV-GFP-miR-107) to clarify the role of miR-107 in tumor angiogenesis in mice. Overexpression of miR-107 decreases HIF-1β protein expression and hypoxic signaling. Interestingly, overexpression of miR-107 in human colon cancer HCT116 (WT) cells and HCT116 (p53 KO) cells suppresses tumor size. Overexpression of miR-107 in HCT116 (p53 KO) cells decreased the number of vessels but no significant amount in HCT116 (WT). They also clarify the relation between hypoxic-regulated gene VEGF and miR-107. miR-107 decreased VEGF expression in tumors from nude mice implanted with HCT116 cells transduced with LV-GFP-miR-107. In human colon cancer specimens, expression of higher VEGF is in the low miR-107 group and is lower in the high miR-106 group. These results indicate that miR-107 can mediate p53 regulation of hypoxic signaling and tumor angiogenesis through inhibits HIF-1β.

 

References:

1.       Chang T. C., et al.Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell. 26, 745-752 (2007).

2.       Bartel D. P. MicroRNAs: target recognition and regulatory functions. Cell. 136, 215-233 (2009).