期刊
DNA AND CELL BIOLOGY
卷 39, 期 12, 页码 2166-2173出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/dna.2020.5771
关键词
lncRNA; HOTAIR; breast cancer; EZH2; radioresistance; DNA damage
资金
- Bengbu Medical College [BYKF1783]
- National Natural Science Foundation of China [30870583, 31501159, 81872495, 81673026, 82070687]
- Youth Teachers Fund of Peking Union Medical College [2014zlgc0755]
- Tianjin Nature Science Foundation [15JCYBJC25400, 16JCQNJC12100, 16JCQNJC13100, 17JCQNJC10100]
- Tianjin Science and Technology Key Project on Chronic Diseases Prevention and Treatment [16ZXMJSY00020]
- Special Program of Talents Development for Excellent Youth Scholars in Tianjin, China [TJTZJH-QNBJRC-2-9]
- Science Foundation from Tianjin Medical University [2015KYZQ05]
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.
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