机构:[1]Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004[2]Department of Radiation Oncology and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000[3]Department of Radiation Oncology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000[4]Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
Esophageal cancer (EC) is one of the leading causes of death among malignancies. Radiotherapy for esophageal squamous cell carcinoma (ESCC) patients is limited by resistance to ionizing radiation (IR). An increasing body of evidence has demonstrated that aberrant expression of microRNA-301a (miR-301a) contributes to cancer progression and sensitivity to radiation. The aim of the present study was to investigate the exact functions and potential mechanisms of miR-301a in ESCC radioresistance. Initially, the miR-301a-transfected radioresistant ESCC cells KYSE-150R exhibited a decreased proliferation rate, and enhanced radiosensitivity and migration, whereas downregulation of miR-301a in radiosensitive KYSE-150 cells produced the opposite results. miR-301a regulates WNT1 expression at both the mRNA and protein levels. Furthermore, dual-luciferase reporter assays revealed that WNT1 was a target gene of miR-301a. In addition, the expression of miR-301a markedly affected the expression of Wnt/-catenin-related proteins such as -catenin and cyclin D1. Finally, overexpression of miR-301a inhibited epithelial-mesenchymal transition (EMT) conversion by directly targeting Snail and vimentin in radioresistant-ESCC cell lines; however, no inhibitory effects were exerted on Twist. Collectively, these results indicated that miR-301a increased the radiosensitivity and inhibited the migration of radioresistant-ESCC cells by targeting WNT1, thereby inactivating the Wnt/-catenin signaling pathway and EMT reversal. Thus, miR-301a may be a potential therapeutic target for the treatment of EC radioresistance.
基金:
The present study was supported by the Natural Science
Foundation of Zhejiang Province (grant nos. LQ15H160013,
LY17H160051 and LY15H280013) and the Natural Science
Foundation of China (grant no. 81602658).
第一作者机构:[1]Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004[2]Department of Radiation Oncology and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000
通讯作者:
通讯机构:[*1]Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Road, Suzhou, Jiangsu 215004, P.R. China[*2]Department of Radiation Oncology and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Lane, Wenzhou, Zhejiang 325000, P.R. China
推荐引用方式(GB/T 7714):
HUAFANG SU,YOUYI WU,YA FANG,et al.MicroRNA-301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells[J].ONCOLOGY REPORTS.2019,41(1):599-607.doi:10.3892/or.2018.6799.
APA:
HUAFANG SU,YOUYI WU,YA FANG,LANXIAO SHEN,ZHENGHUA FEI...&MING CHEN.(2019).MicroRNA-301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells.ONCOLOGY REPORTS,41,(1)
MLA:
HUAFANG SU,et al."MicroRNA-301a targets WNT1 to suppress cell proliferation and migration and enhance radiosensitivity in esophageal cancer cells".ONCOLOGY REPORTS 41..1(2019):599-607