Functional restoration experiments were carried out to explore the regulatory mechanism of miR-205-5p in PTX sensitivity and cell growth. miR-205-5p was upregulated in EC tissues and cell lines compared with respective control.
Moreover, miR-205 was found to negatively regulate PTEN expression and lead to autophagy and activation of the AKT/mTOR pathway in PR cells, and PTEN protein levels significantly decreased with development of progesterone resistance in endometrial cancer cells.
We found that systemic administration of miR-205-LNA-inhibitor was technically possible, and exerted inhibitory effect on endometrial cancer xenograft growth in vivo with only mild toxic effects in treated animals.In conclusion our results suggest that systemic delivery of miR-205-LNA-inhibitor is feasible, devoid of significant toxicity, and could be a promising treatment strategy for endometrial cancer.
For the first time, we demonstrate that the expression of PTEN is directly regulated by miR-205 in endometrial cancer cells and leads the inhibition of cellular apoptosis.
After transfection of a miR-205 inhibitor, the expression of miR-205 in endometrial cancer cell line RL95-2 cells decreased whereas its predicted target gene, JPH4, showed increased protein expression.