siRNA knockdown of ZEB1 and ZEB2 impaired As-transformed p53lowHBEC migration and invasion.
CONCLUSIONS: Akt activation plays a critical role in enabling As-transformed HBEC migration and invasion by promoting ZEBl and ZEB2 expression.
Moreover, we demonstrated that Akt activation drives As-transformed HBEC migration and invasion by promoting the expression of EMT-inducing transcription factors zinc-finger E-box-binding homeobox factor 1 (ZEBl)and ZEB2.
Negative control small interfering RNA (siRNA) and ON-TARGETpIus SMARTpool siRNA for ZEBl and ZEB2 were obtained from Thermo Scientific Dharmacon (Lafayette, CO, USA).
Akt activation enables As-transformed HBEC migration and invasion via promoting ZEB1 and ZEB2 expression.
To decermine the role oi ZEBl and ZEB2 in As-rransformed [p53.
By overexpressing miR-200b, applying pharmacological inhibitors to inactivate Akt or Erkl/2, and siRNA knockdown of the expression of ZEB1 and ZEB2, we established that it is the activation of Akt, and not Erkl/2, that enables As-transformed HBECs to migrate and invade.
Moreover, inactivation of Akt by treatment with a PI3K inhibitor or an Akt inhibitor similarly and significantly reduced the expression of ZEB1 and ZEB2, cell migration, and invasion.
ZEB1 and ZEB2 are EMT-inducing transcription factors (Peinado et al.
Using pregnant mice as well as human uterine tissue, the researchers have uncovered a feedback cycle involving microRNAs, proteins called ZEB1 and ZEB2, and the pregnancy-maintaining hormone progesterone, as well as genes and other factors that control contraction of the uterus.
The miR-200s block the production of two proteins called ZEB1 and ZEB2.