MiR-498/DNMT3b Axis Mediates Resistance to Radiotherapy in Esophageal Cancer Cells.

Abstract

Objective: To explore the role of miR-498 in the radiotherapy resistance of esophageal cancer (EC) and its underlying mechanism. Methods: In vivo models of EC tissues with radioresistance or radiosensitivity were isolated from 72 EC patients who received radiotherapy. In vitro models were established after irradiation of KYSE30 cells. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were employed to measure the expression levels of miR-498 and DNMT3b in EC cells sensitive or resistant to irradiation. Then, protein expression of DNMT3b was verified by immunohistochemistry. The cell viability, colony formation rate, and cell apoptotic rate of EC were correspondingly assessed by CCK-8, colony formation assay, and Annexin V/PI (propidium iodide) double staining. Western blot was utilized to perform the expression levels of PI3K, p-PI3K, AKT, and p-AKT in EC cell lines after irradiation. Results: Highly expressed DNMT3b and lowly expressed miR-498 were found in EC tissues. EC tissues with radiosensitivity had higher miR-498 level and lower DNMT3b expression than EC tissues with radioresistance. Overexpression of miR-498 or knockdown of DNMT3b enhanced the radiosensitivity of EC cells. DNMT3b was a target gene of miR-498. DNMT3b diminished the radiosensitization of miR-498 in EC cells. Conclusions: MiR-498 enhances the sensitivity of EC cells to radiation by DNMT3b inhibition, and exerts biological functions by inactivating the PI3K/AKT signaling pathway.