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长链非编码RNA通过EZH2促进乳腺癌的DNA修复和放射抗性。

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

作者信息

Qian Liyu, Fei Qiaoman, Zhang Haoran, Qiu Manman, Zhang Bo, Wang Qin, Yu Yang, Guo Chenxu, Ren Yu, Mei Mei, Zhang Ling, Zhu Yu, Yang Bing

机构信息

Department of Tumor Surgery and The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

School of Basic Medical Science, Tianjin Medical University, Tianjin, China.

出版信息

DNA Cell Biol. 2020 Nov 2. doi: 10.1089/dna.2020.5771.

DOI:10.1089/dna.2020.5771
PMID:33136445
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 () expression increased in invasive ductal carcinoma (IDC) tissue. The irradiation effect of 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. , upregulated in IDC of breast cancer tissue, could promote breast cancer cell proliferation by regulating cell cycle and apoptosis. Overexpression of 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 (). Meanwhile, we found that could facilitate recruitment of to the Avian Myelocytomatosis Viral Oncogene Homolog (MYC) promoter. is an important modulator not only to the prognostic of breast cancer, but also a good marker for radiotherapy.

摘要

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,而放射抗性可能是肿瘤复发的一个重要因素。我们观察到HOX反义基因间RNA()在浸润性导管癌(IDC)组织中的表达增加。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)测定、细胞周期和凋亡分析以及裸鼠异种移植来检测的辐射效应。蛋白质免疫印迹法、RNA下拉分析和RNA免疫沉淀用于机制研究。在乳腺癌组织的IDC中上调,可通过调节细胞周期和凋亡来促进乳腺癌细胞增殖。的过表达促进了DNA损伤修复因子KU70、KU80、DNA-PKs和ATM的表达,而这些可被小分子量的zeste同源物2()增强子抑制剂所阻碍。同时,我们发现可促进与禽成髓细胞瘤病毒癌基因同源物(MYC)启动子的结合。不仅是乳腺癌预后的重要调节因子,也是放疗的良好标志物。

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