@Article{096504019X15518706875814,
AUTHOR = {Linglan Gu, Yi Shi, Weimin Xu, Yangyang Ji},
TITLE = {PPARb/d Agonist GW501516 Inhibits Tumorigenesis and Promotes  Apoptosis of the Undifferentiated Nasopharyngeal Carcinoma C666-1  Cells by Regulating miR-206},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {8},
PAGES = {923--933},
URL = {http://www.techscience.com/or/v27n8/48621},
ISSN = {1555-3906},
ABSTRACT = {In previous investigations, we reported that peroxisome proliferator-activated receptor / (PPAR / ) activation by GW501516 inhibits proliferation and promotes apoptosis in the undifferentiated C666-1 nasopharyngeal carcinoma (NPC) cells by modulating caspase-dependent apoptotic pathway. In the present study, the 
mechanism by which GW501516 induces apoptosis was explored from the perspective of microRNA (miRNA) 
expression. Among the assayed miRNAs that were involved in regulating the expression of antiapoptotic protein Bcl-2, miR-206 was increased significantly and specifically by GW501516 in C666-1 cells at both the in 
vitro level and at the in vivo xenograft samples. The induction on miR-206 expression caused by GW501516 
was capable of being antagonized by the PPAR / antagonist GSK3787 and AMPK antagonist dorsomorphin 
in C666-1 cells. GW501516’s suppression on the growth and apoptosis of C666-1 cells was found to be dependent on the presence of miR-206. miR-206 overexpression resulted in suppressed proliferation and colony 
formation ability, and further triggered increased apoptosis in C666-1 cells in a caspase-dependent manner. 
The expression of cleaved caspase 3 and caspase 9, and the ratio of Bax to Bcl-2 were elevated remarkably by 
miR-206. Consistent with the in vitro result, miR-206 was corroborated to suppress the ectopic NPC xenograft 
tumorigenesis that derived from the C666-1 cells in BALB/c nu/nu mice. Taken together, the current data demonstrated that miR-206 plays a critical role in the direct apoptosis-promoting effect induced by GW501516 in 
C666-1 cells. Furthermore, the emphasized tumor-suppressive role of miR-206 in the C666-1 cells indicates 
that it has the potential to provide a new therapeutic approach for the undifferentiated NPC.},
DOI = {10.3727/096504019X15518706875814}
}