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用寡核苷酸拮抗剂靶向长链非编码RNA ASBEL用于乳腺癌治疗。

Targeting long non-coding RNA ASBEL with oligonucleotide antagonist for breast cancer therapy.

作者信息

Xia Yang, Xiao Xiangqian, Deng Xiongwei, Zhang Fang, Zhang Xiaofei, Hu Qin, Sheng Wang

机构信息

College of Life Science and Bioengineering, Beijing University of Technology, PR China.

College of Life Science and Bioengineering, Beijing University of Technology, PR China.

出版信息

Biochem Biophys Res Commun. 2017 Aug 5;489(4):386-392. doi: 10.1016/j.bbrc.2017.05.136. Epub 2017 May 25.

Abstract

Long non-coding RNAs (lncRNAs) are defined as a class of RNA transcripts longer than 200 nucleotides encoded by mammalian genomes that lack protein-coding potential. LncRNA ASBEL has been identified as an anti-sense transcript of BTG3 (B cell translocation gene 3) gene, which encodes an anti-proliferation protein. Remarkable down-regulation of BTG3 has been reported in triple-negative breast cancer (TNBC). In the present study, a number of single-stranded modified anti-sense DNA oligonucleotides (antago) were designed, synthesized and screened for specific lncRNA ASBEL knockdown. We showed here that anti-ASBEL antago played a significant tumor suppressive role in TNBC by effective down-regulating lncRNA ASBEL, which in turn led to increased BTG3 expression. The obtained data suggest lncRNA ASBEL as a novel therapeutic target in TNBC.

摘要

长链非编码RNA(lncRNAs)被定义为一类由哺乳动物基因组编码的、长度超过200个核苷酸且缺乏蛋白质编码潜力的RNA转录本。LncRNA ASBEL已被鉴定为BTG3(B细胞易位基因3)基因的反义转录本,该基因编码一种抗增殖蛋白。据报道,三阴性乳腺癌(TNBC)中BTG3显著下调。在本研究中,设计、合成并筛选了多种单链修饰反义DNA寡核苷酸(反义寡核苷酸)以特异性敲低lncRNA ASBEL。我们在此表明,抗ASBEL反义寡核苷酸通过有效下调lncRNA ASBEL在TNBC中发挥显著的肿瘤抑制作用,这反过来又导致BTG3表达增加。所得数据表明lncRNA ASBEL是TNBC中的一个新的治疗靶点。

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