MicroRNA-621 Acts as a Tumor Radiosensitizer by Directly Targeting SETDB1 in Hepatocellular Carcinoma

Autor: Yingjie Shao, Zhonghua Ning, Xing Song, Wendong Gu, Wenjie Jiang, Jingting Jiang, Yuan Chen
Rok vydání: 2019
Předmět:
p53
Untranslated region
Radiation-Sensitizing Agents
Radiosensitizer
Poor prognosis
Carcinoma
Hepatocellular
medicine.medical_treatment
Mice
Nude
Mice
03 medical and health sciences
0302 clinical medicine
Cell Line
Tumor
Drug Discovery
microRNA
SETDB1
Genetics
medicine
Animals
Humans
Radiosensitivity
Microwaves
neoplasms
Molecular Biology
Cell Proliferation
030304 developmental biology
Pharmacology
0303 health sciences
business.industry
Liver Neoplasms
Tumor therapy
Hep G2 Cells
Histone-Lysine N-Methyltransferase
hepatocellular carcinoma
miR-621
medicine.disease
digestive system diseases
Gene Expression Regulation
Neoplastic
Radiation therapy
MicroRNAs
radiosensitivity
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Cancer research
Molecular Medicine
Original Article
business
Signal Transduction
Zdroj: Molecular Therapy
ISSN: 1525-0016
DOI: 10.1016/j.ymthe.2018.11.005
Popis: Radiotherapy is one of the most important treatment methods of tumors. However, the application of radiotherapy in hepatocellular carcinoma (HCC) is limited due to the low tolerance of normal liver cells for radiation and inherent radiation resistance in HCC. With the in-depth study of microRNAs (miRNAs) in tumor therapy, the regulation of tumor radiosensitivity by miRNAs has been a research hotspot in recent years. In the present study, the expression of miR-621 was lower in HCC tissues and cells, and such low expression of miR-621 was associated with poor prognosis in HCC patients. In addition, in vivo and in vitro assays confirmed that the high expression of miR-621 could significantly enhance the radiosensitivity of HCC. Moreover, the expressions of miR-621 and SETDB1 in HCC tissues were negatively correlated. Dual-luciferase reporter assays indicated that miR-621 could directly target the 3′ UTR of SETDB1. In addition, miR-621 enhanced the radiosensitivity of HCC cells via directly inhibiting SETDB1. Besides, the miR-621 and/or SETDB1 axis improved the radiosensitivity of HCC cells via activating the p53-signaling pathway. Taken together, miR-621 and/or SETDB1 might be used as a novel therapeutic target for the treatment of HCC.
The application of radiotherapy in hepatocellular carcinoma (HCC) is limited due to the low tolerance of normal liver cells for radiation and inherent radiation resistance in HCC. Gu and colleagues found that the miR-621 and/or SETDB1 axis could improve the radiosensitivity of HCC cells via activating the p53-signaling pathway.
Databáze: OpenAIRE
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