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.

中文翻译：

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lncRNA HOTAIR 通过 EZH2 促进乳腺癌的 DNA 修复和放射抗性


越来越多的证据表明，长链非编码RNA在人类疾病中发挥着重要作用，放射抗性可能是肿瘤复发的重要因素。我们观察到 HOX 反义基因间 RNA ( HOTAIR ) 在浸润性导管癌 (IDC) 组织中表达增加。通过3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四唑(MTS)法检测HOTAIR的照射效果、细胞周期和细胞凋亡分析和裸鼠异种移植。 Western blot、RNA Pulldown 测定和 RNA 免疫沉淀用于机制研究。 HOTAIR在乳腺癌组织IDC中表达上调，可通过调节细胞周期和凋亡促进乳腺癌细胞增殖。 HOTAIR的过表达促进了 DNA 损伤修复因子 KU70、KU80、DNA-PK 和 ATM 的表达，并且这些可以被 zeste 同源物增强子 2 ( EZH2 ) 的小分子抑制剂阻碍。同时，我们发现HOTAIR可以促进EZH2招募至禽骨髓细胞瘤病毒癌基因同源物 (MYC) 启动子。 HOTAIR不仅是乳腺癌预后的重要调节剂，也是放射治疗的良好标志物。