lncRNA HOTAIR Promotes DNA Repair and Radioresistance of Breast Cancer via EZH2

被引：46

作者：

Qian, Liyu ^{[1
]}

Fei, Qiaoman ^{[3
]}

Zhang, Haoran ^{[2
]}

Qiu, Manman ^{[3
]}

Zhang, Bo ^{[3
]}

Wang, Qin ^{[4
]}

Yu, Yang ^{[5
]}

Guo, Chenxu ^{[1
]}

Ren, Yu ^{[3
]}

Mei, Mei ^{[3
]}

Zhang, Ling ^{[3
]}

Zhu, Yu ^{[6
]}

Yang, Bing ^{[3
]}

机构：

[1] Bengbu Med Coll, Affiliated Hosp 1, Dept Tumor Surg, Bengbu, Peoples R China

[2] Bengbu Med Coll, Affiliated Hosp 1, Dept Med Oncol, Bengbu, Peoples R China

[3] Tianjin Med Univ, Sch Basic Med Sci, Tianjin 300070, Peoples R China

[4] Chinese Acad Med Sci & Peking Union Med Coll, Inst Radiat Med, Tianjin Key Lab Radiat Med Mol Nucl Med, Tianjin, Peoples R China

[5] Tianjin Med Univ, Sch Pharm, Tianjin, Peoples R China

[6] Tianjin Haihe Hosp, Dept Clin Lab, Tianjin 300350, Peoples R China

来源：

DNA AND CELL BIOLOGY | 2020年 / 39卷 / 12期

基金：

中国国家自然科学基金;

关键词：

lncRNA; HOTAIR; breast cancer; EZH2; radioresistance; DNA damage; RADIOSENSITIVITY; APOPTOSIS;

D O I：

10.1089/dna.2020.5771

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mounting evidence shows that long noncoding RNAs play important roles in human diseases and radioresistance could be an important factor for tumor recurrence. We observed that HOX antisense intergenic RNA (HOTAIR) expression increased in invasive ductal carcinoma (IDC) tissue. The irradiation effect of HOTAIR was detected by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, cell cycle and apoptosis analysis, and xenografts in nude mice. Western blot, RNA pulldown assay, and RNA immunoprecipitation were used for mechanistic studies. HOTAIR, upregulated in IDC of breast cancer tissue, could promote breast cancer cell proliferation by regulating cell cycle and apoptosis. Overexpression of HOTAIR promoted DNA damage repair factors KU70, KU80, DNA-PKs, and ATM expression, and these could be impeded by small molecular inhibitors of enhancer of zeste homolog 2 (EZH2). Meanwhile, we found that HOTAIR could facilitate recruitment of EZH2 to the Avian Myelocytomatosis Viral Oncogene Homolog (MYC) promoter. HOTAIR is an important modulator not only to the prognostic of breast cancer, but also a good marker for radiotherapy.

引用

页码：2166 / 2173

页数：8

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