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长链非编码 RNA CERS6-AS1 通过海绵吸附 miR-125a-5p 促进乳腺癌细胞增殖,从而上调 BAP1 表达。

lncRNA CERS6-AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR-125a-5p to upregulate BAP1 expression.

机构信息

Anhui Provincial Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, Anhui, China.

Department of Clinical Diagnostics, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui, China.

出版信息

Mol Carcinog. 2020 Oct;59(10):1199-1208. doi: 10.1002/mc.23249. Epub 2020 Aug 18.

DOI:10.1002/mc.23249
PMID:32808708
Abstract

Long noncoding RNAs (lncRNAs) can act as oncogene and tumor suppressor genes in many types of cancers including breast cancer (BC). Our previous study has indicated microRNA (miR)-125a-5p was downregulated and function as a tumor suppressor in BC. However, its upstream regulation mechanism is still unclear. In this study, we used bioinformatics algorithms, RNA pulldown assay, and dual-luciferase reports assay to predict and confirm lncRNA CERS6-AS1 interacted with miR-125a-5p. Then we found CERS6-AS1 was upregulated in BC tissues. Experimental results of tumor growth in nude mice show that CERS6-AS1 promotes tumor growth. Furthermore, CERS6-AS1 regulated BC susceptibility gene 1-associated protein 1 (BAP1) expression via sponging miR-125a-5p via Western blot analysis and quantitative polymerase chain reaction arrays. Finally, we showed that miR-125a-5p had opposing effects to those of CERS6-AS1 on BC cells, demonstrating that CERS6-AS1 may promote cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p. Our results indicated CERS6-AS1 promote BC cell proliferation and inhibit cell apoptosis via sponging miR-125a-5p to upregulate BAP1 expression.

摘要

长链非编码 RNA(lncRNA)在多种癌症中可作为癌基因和抑癌基因发挥作用,包括乳腺癌(BC)。我们之前的研究表明 microRNA(miR)-125a-5p 在 BC 中下调并作为肿瘤抑制因子发挥作用。然而,其上游调控机制尚不清楚。在本研究中,我们使用生物信息学算法、RNA 下拉实验和双荧光素酶报告实验预测并证实 lncRNA CERS6-AS1 与 miR-125a-5p 相互作用。然后我们发现 CERS6-AS1 在 BC 组织中上调。裸鼠肿瘤生长的实验结果表明 CERS6-AS1 促进肿瘤生长。此外,通过 Western blot 分析和定量聚合酶链反应(qPCR)芯片实验,我们发现 CERS6-AS1 通过海绵吸附 miR-125a-5p 调节 BC 易感性基因 1 相关蛋白 1(BAP1)的表达。最后,我们表明 miR-125a-5p 对 BC 细胞的作用与 CERS6-AS1 相反,表明 CERS6-AS1 可能通过海绵吸附 miR-125a-5p 促进细胞增殖并抑制细胞凋亡。我们的研究结果表明,CERS6-AS1 通过海绵吸附 miR-125a-5p 上调 BAP1 表达,从而促进 BC 细胞增殖并抑制细胞凋亡。

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