MiR-7a is an important mediator in Fas-associated protein with death domain (FADD)-regulated expression of focal adhesion kinase (FAK)
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Yingting Liu1, Hongen Cui1, Xianjie Huang1, Bo Zhu1, Shengwen Guan2, Wei Cheng1, Yueyang Lai1, Xiaoxin Zhang1, Zi-Chun Hua1,3,4
1The State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210032, China
2Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou, 213164, China
3The State Key Lab of Natural Medicines, China Pharmaceutical University, Nanjing, 210017, China
4The State Key Laboratory of Bioelectronics, Southeast University, Nanjing, 210008, China
Zi-Chun Hua, email: [email protected]
Keywords: FADD, FAK, miR-7a, melanoma, migration
Received: December 29, 2015 Accepted: May 08, 2016 Published: June 06, 2016
Fas-associated protein with death domain (FADD), a classical adaptor protein mediating apoptotic stimuli-induced cell death, has been reported to engage in several non-apoptotic processes such as T cell and cardiac development and tumorigenesis. Recently, there are several reports about the FADD’s involvement in cell migration, however the underlying mechanism remains elusive. Here, we present a new finding that FADD could regulate the expression of FAK, a non-receptor protein tyrosine kinase overexpressed in many cancers, and played an important role in cell migration in murine MEF and melanoma cells with different metastatic potential, B16F10 and B16F1. Moreover, miR-7a, a tumor suppressor which prohibits cell migration and invasion, was up-regulated in FADD-deficient cells. And FAK was verified to be the direct target gene of miR-7a in B16F10 cells. Furthermore, we demonstrate that miR-7a was a necessary mediator in FADD-regulated FAK expression. In contrast to its classical apoptotic role, FADD interference could reduce the rate of cell migration, which could be rescued by inhibiting miR-7a expression. Taken together, our data provide a novel explanation regarding how FADD regulates cell migration in murine melanoma cells.
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