Abstract 1066: MicroRNA-125b mediated par2 activation-induced cell migration

Abstract

Abstract Backgrounds: Tumor microenvironment plays a promoting role in cancer metastasis. As important component of the microenvironment, some proteinases regulate tumorigenesis through selective activation of proteinase activated receptor 2 (PAR2). Our previous study demonstrated that overexpression of PAR2 was significantly correlated with lymphatic metastasis in colorectal cancers. Aims: To identify whether and by what mechanisms PAR2 promotes cell migration. Methods and Results: Activation of PAR2 with activating peptide (PAR2-AP, 100μM) dramatically increased cell migration in different cell lines which was measured by transwell assay. In addition, miR-125b was reduced at 6 and 12 hours, while the migration was observed at 12 hours after PAR2-AP treatment. Consistent with previous report, inhibitor of miR-125b dramatically prompted cell migration in A549 cells. To test whether the downregulation of miR-125b mediates PAR2-induced migration, miR-125b mimic was transfected into A549 cells to recover the reduction of miR-125b induced by PAR2 activation. It was showed that miR-125b mimic also successfully blocked PAR2-induced cell migration. Furthermore, pretreatment with 5-aza-CdR (5umol/L) for 24h dramatically prevented PAR2-induced downregulation of miR-125b in A549 cells. It suggests that methylation of miR125b promoter may be the mechanism by which PAR2 repressed the expression of miR-125b. On the other hand, the data showed that Lin28B was increased dramatically by miR-125b inhibitor, which indicated that Lin28B may be the downstream target gene of miR-125b in A549 cells. Most importantly, we found that upregulation of PAR2 and downregulation of miR-125b were significantly correlated with lymphatic metastasis in human colorectal cancer specimens. Conclusion: Our study demonstrated that activation of PAR2 promotes cell migration through miR-125b, which may contribute to PAR2-related lymphatic metastasis in CRC. Citation Format: LAN YANG. MicroRNA-125b mediated par2 activation-induced cell migration. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1066. doi:10.1158/1538-7445.AM2014-1066