机构：[1]Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China[2]Department of Oncology, The Fourth Hospital, Hebei Medical University, Shijiazhuang, China临床科室肿瘤内科河北医科大学第四医院[3]Lab of Pathology, Hebei Medical University, Shijiazhuang, China[4]Department of Pharmacology, Hebei Medical University, Shijiazhuang, China
Background Our recent studies have indicated that miR-153-3p is downregulated in the esophageal squamous cell carcinoma (ESCC) cell lines and tissues. Upregulation of miR-153-3p was found to inhibit migration and invasion of ESCC cells. However, whether miR-153-3p regulates the cisplatin sensitivity in ESCC cells remains unclear. In this study, we explored whether and how miR-153-3p regulates the proliferation and confers cisplatin resistance in ESCC by targeting the Nrf-2 protein. Methods Eca109 cell line was transfected with microRNA-153-3p mimics or Nrf-2siRNA and cell proliferation and cisplatin resistance were studied. A dual-luciferase reporter assay was performed on Eca109 cells cotransfected with the wild-type/mutant 3 ' UTR sequences of Nrf-2 and control or microRNA-153-3p mimics. We determined the correlation between microRNA-153-3p and Nrf-2 expression in human ESCC samples and explored the effect of Nrf-2 in the overall survival rate of ESCC patients. Results MiR-153-3p significantly suppressed cell proliferation and increased the sensitivity of Eca-109 cells to cisplatin. MiR-153-3p showed a negative correlation with Nrf-2 in human esophageal carcinoma tissues. MiR-153-3p suppressed the expression of Nrf-2 via binding to its 3 '-UTR region. Furthermore, inhibition of Nrf-2 also decreased cell proliferation and increased the sensitivity of Eca109 cells to cisplatin. High expression of Nrf-2 in human ESCC samples was associated with poor overall survival of ESCC patients. Conclusion MiR-153-3p inhibits cell proliferation and confers cisplatin resistance by downregulating Nrf-2 expression in Eca-109 cells. Thus, miR-153-3p/Nrf-2 may play an important role in conferring cisplatin resistance in ESCC. Nrf-2 appears to be a promising therapeutic target for ESCC.
基金：
This work was supported by the National Natural Science
Foundation of China (31570894; 81670939; 81672706), the Foundation of Hebei Educational Committee, China
(SLRC2017045; key program, ZD2015010), and the Natural
Science Foundation for Distinguished Young Scholars of
Hebei Province, China (H2018206120, H.S; H2017206332,
J.Z).
第一作者机构：[1]Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China[2]Department of Oncology, The Fourth Hospital, Hebei Medical University, Shijiazhuang, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pathology, The Second Hospital, Hebei Medical University, Shijiazhuang, China[3]Lab of Pathology, Hebei Medical University, Shijiazhuang, China[*1]Department of Pathology, The Second Hospital, Hebei Medical University, 215 Heping West Rd, Shijiazhuang, Hebei 050000, China.
推荐引用方式(GB/T 7714)：
Zuo Jing,Zhao Mei,Fan Zhisong,et al.MicroRNA-153-3p regulates cell proliferation and cisplatin resistance via Nrf-2 in esophageal squamous cell carcinoma[J].THORACIC CANCER.2020,11(3):738-747.doi:10.1111/1759-7714.13326.
APA：
Zuo, Jing,Zhao, Mei,Fan, Zhisong,Liu, Bowei,Wang, Yudong...&Shen, Haitao.(2020).MicroRNA-153-3p regulates cell proliferation and cisplatin resistance via Nrf-2 in esophageal squamous cell carcinoma.THORACIC CANCER,11,(3)
MLA：
Zuo, Jing,et al."MicroRNA-153-3p regulates cell proliferation and cisplatin resistance via Nrf-2 in esophageal squamous cell carcinoma".THORACIC CANCER 11..3(2020):738-747
