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

Abstract

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.

Keywords: DNA damage; EZH2; HOTAIR; breast cancer; lncRNA; radioresistance.