ANTAGONISTS
Loss of skeletal muscle mass and strength is a central feature of traumatic injuries and degenerative myopathies. Unfortunately, pharmacological interventions often fail to stem the long-term decline in quality of life. REV-ERB-mediated reduced gene suppression in cultured c2c12 myoblasts has been shown to stimulate myoblast differentiation. However, the mechanisms that allow REV-ERB to pleiotropically inhibit muscle differentiation are not well known. Thus, a study elucidated the role of REV-ERB in regulating muscle differentiation and regeneration in vivo. The REV-ERB α/β regulation mechanism for muscle differentiation and regeneration was analyzed. Myoblast analysis showed that REV-ERB α did not transcriptionally regulate muscle differentiation through cognate elements REV-ERB/​​ror-response, but through a possible interaction with the regulator of nf-y cell fate in ccaat motifs. Muscle differentiation is stimulated by the release of REV-ERB from CCAAT motifs in the elements promoting and enhancing various myogenic proteins. Therefore, the interruption of REV-ERB activity in the injured muscle accelerates regenerative muscle repair/differentiation through the transcriptional detoxification of myogenic programs. Thus, REV-ERB can be a potent therapeutic target for a multitude of muscle disorders [57].
In previous investigations, we have reported that activation of the β/δ receptor activated by the peroxisome proliferator by gw501516 inhibits proliferation and promotes apoptosis in the undifferentiated cells of c666-1 nasopharyngeal carcinoma (NPC) modulating the caspase-dependent apoptotic pathway. Thus, a study explored the mechanism by which gw501516 induces apoptosis through the expression of the microwave (mirna). Among the mirnas analyzed involved in regulating the expression of the anti-apoptotic protein bcl-2, mir-206 increased significantly and specifically by gw501516 in c666-1 cells, both in vitro and in xenograft samples in vivo . The induction in mir-206 expression caused by gw501516 was able to be antagonized by the antagonist gsk3787 of pparβ/δ and by the dorsomorphine antagonist of ampk in cells c666-1. Suppression of gw501516 in the growth and apoptosis of c666-1 cells has been found to depend on the presence of mir-206 [58].
The overexpression of mir-206 resulted in suppressed proliferation and the ability to form colonies, in addition to triggering 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 increased notably by mir-206. Current data has shown that mir-206 plays a critical role in the direct promotion effect of gw501516-induced apoptosis in c666-1 cells. Also, the emphasized tumor-suppressing role of mir-206 in c666-1 cells indicates that it has the potential to provide a new therapeutic approach [58].