MiR-139 Affects Radioresistance in Esophageal Cancer by Targeting the PDK1/AKT/Cyclin D1 Signaling Pathway

We explored the mechanism by which miR-139 modulates radioresistance of esophageal cancer (EC). The radioresistant cell line KYSE150R was obtained from the parental KYSE150 cell line by fractionated irradiation (15×2 Gy; total dose of 30 Gy). The cell cycle was assessed by flow cytometry. A gene profiling study was conducted to detect the expression of genes related to the radioresistance of EC. In the KYSE150R line, flow cytometry revealed increased number of G1-phase cells and decreased number of G2-phase cells; the expression of miR-139 increased. Knockdown of miR-139 decreased radioresistance and changed the distribution of cell cycle phases in KYSE150R cells. Western blotting showed that miR-139 knockdown increased the expression levels of cyclin D1, p-AKT, and PDK1. However, PDK1 inhibitor GSK2334470 reversed this effect for p-AKT and cyclin D1 expression. A luciferase reporter assay indicated that miR-139 directly bound to the PDK1 mRNA 3'-UTR. Analysis of the clinical data from 110 patients with EC showed an association of miR-139 expression with the TNM stage and the effect of therapy. MiR-139 expression significantly correlated with EC and progression-free survival. In conclusion, miR-139 enhances the radiosensitivity of EC by regulating the cell cycle through the PDK1/Akt/Cyclin D1 signaling pathway.

 

Comments：

The study investigated the mechanism by which miR-139 modulates radioresistance in esophageal cancer (EC). The researchers used the radioresistant cell line KYSE150R, obtained from the parental KYSE150 cell line by fractionated irradiation. They conducted a gene profiling study to detect the expression of genes related to the radioresistance of EC and assessed the cell cycle by flow cytometry.

In the KYSE150R cell line, the researchers found an increased number of G1-phase cells and decreased number of G2-phase cells, along with an increase in miR-139 expression. Knockdown of miR-139 decreased radioresistance and changed the distribution of cell cycle phases in KYSE150R cells. The researchers also found that miR-139 directly bound to the PDK1 mRNA 3'-UTR, and its knockdown increased the expression levels of cyclin D1, p-AKT, and PDK1. The PDK1 inhibitor GSK2334470 reversed the effect of miR-139 knockdown on p-AKT and cyclin D1 expression.

Analysis of clinical data from 110 EC patients showed an association of miR-139 expression with TNM stage and the effect of therapy. MiR-139 expression significantly correlated with EC and progression-free survival.

In conclusion, the study suggests that miR-139 enhances the radiosensitivity of EC by regulating the cell cycle through the PDK1/Akt/Cyclin D1 signaling pathway.

Related Products

Cat.No.	Product Name	Information
S7087	GSK2334470	GSK2334470 is a novel PDK1 inhibitor with IC50 of ~10 nM in a cell-free assay, with no activity at other close related AGC-kinases.

Related Targets

PDPK1