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Long non-coding RNA H19 regulates proliferation and doxorubicin resistance in MCF-7 cells by targeting PARP1.
Bioengineered ( IF 4.9 ) Pub Date : 2020-05-13 , DOI: 10.1080/21655979.2020.1761512
Yu Wang 1 , Peihong Zhou 2 , Ping Li 3 , Fengxia Yang 3 , Xue-Qiang Gao 1
Affiliation  

Chemoresistance is a major obstacle to effective breast cancer chemotherapy. However, the underlying molecular mechanisms remain unclear. The long noncoding RNA H19 (H19) is involved in various stages of tumorigenesis, however, its role in doxorubicin resistance remains unknown. The goal of this study was to evaluate the role of H19 in the development of doxorubicin-resistant breast cancer. Quantitative real-time PCR (qRT-PCR) analyzed H19 expression in chemotherapy-resistant and sensitive breast cancer tissues. Both knockdown and overexpression of H19 were used to assess the sensitivity to doxorubicin in breast cancer cells in vitro and in vivo. qRT-PCR and Western blot were used to explore the doxorubicin resistance mechanism of H19. We observed that the H19 expression was significantly upregulated in chemotherapy-resistant breast cancer tissues and doxorubicin-resistant breast cancer cell lines. Knockdown of H19 enhanced the sensitivity to doxorubicin both in vitro and in vivo. While H19 overexpression developed doxorubicin-resistant in breast cancer cells both in vitro and in vivo. Furthermore, it was revealed that H19 negatively regulated PARP1 expression in breast cancer cells following doxorubicin treatment. Knockdown of H19 sensitized breast cancer cells to doxorubicin by promoting PARP1 upregulation. H19 overexpression could recapitulate doxorubicin resistance by PARP1 downregulation. Our findings revealed that H19 plays a leading role in breast cancer chemoresistance development, mediated mainly through a H19-PARP1 pathway.

中文翻译:

长链非编码 RNA H19 通过靶向 PARP1 调节 MCF-7 细胞的增殖和阿霉素抗性。

化疗耐药是有效乳腺癌化疗的主要障碍。然而,潜在的分子机制仍不清楚。长链非编码 RNA H19 (H19) 参与肿瘤发生的各个阶段,然而,其在多柔比星耐药中的作用仍然未知。本研究的目的是评估 H19 在阿霉素耐药乳腺癌发展中的作用。定量实时 PCR (qRT-PCR) 分析了化疗耐药和敏感乳腺癌组织中 H19 的表达。H19 的敲低和过表达都用于评估体外和体内乳腺癌细胞对阿霉素的敏感性。qRT-PCR和Western Blot被用来探索H19的多柔比星耐药机制。我们观察到 H19 表达在化疗耐药的乳腺癌组织和多柔比星耐药的乳腺癌细胞系中显着上调。H19 的敲除增强了体外和体内对阿霉素的敏感性。虽然 H19 过表达在体外和体内的乳腺癌细胞中都产生了阿霉素耐药性。此外,发现H19在多柔比星治疗后负调节乳腺癌细胞中的PARP1表达。通过促进 PARP1 上调,H19 的敲低使乳腺癌细胞对阿霉素敏感。H19 过表达可以通过 PARP1 下调重现多柔比星抗性。我们的研究结果表明,H19 在乳腺癌化学抗性发展中起主导作用,主要通过 H19-PARP1 途径介导。
更新日期:2020-05-13
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