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Silencing long non-coding RNA HNF1A-AS1 inhibits growth and resistance to TAM of breast cancer cells via the microRNA-363/SERTAD3 axis
Journal of Drug Targeting ( IF 4.5 ) Pub Date : 2021-05-17 , DOI: 10.1080/1061186x.2021.1878362
Ying Li 1 , Ling Liu 1 , Yidong Lv 2 , Yanwu Zhang 2 , Linlin Zhang 3 , Haiyang Yu 3 , Weifang Tian 1 , Zhan Zhang 4 , Shihong Cui 4
Affiliation  

Abstract

Long non-coding RNAs (lncRNAs) can exert effects on drug resistance of cancer cells. This study investigated the role of lncRNA HNF1A-antisense 1 (HNF1A-AS1) in growth and Tamoxifen (TAM) sensitivity of breast cancer (BC) cells. HNF1A-AS1 expression was promoted in BC cells and tissues. BC cells with HNF1A-AS1 silencing were constructed to detect cell proliferation. TAM resistant cell line with HNF1A-AS1 silencing and parent cell line with overexpressed HNF1A-AS1 were constructed to measure drug resistance. Silencing HNF1A-AS1 reduced proliferation and TAM resistance of BC cells. The downstream microRNAs (miRs) of HNF1A-AS1 and its targets were figured out and their functions in TAM resistance of BC cells were identified. HNF1A-AS1 sponged miR-363 to promote SERTAD3 expression. Downregulation of miR-363 or upregulation of SERTAD3 stimulated TAM resistance of BC cells. The findings in vitro were reproduced in in vivo experiments. It could be concluded that silencing HNF1A-AS1 inhibited growth and drug resistance to TAM of BC cells through the miR-363/SERTAD3 axis and the inactivation of the TGF-β/Smad pathway.



中文翻译:

沉默长链非编码 RNA HNF1A-AS1 通过 microRNA-363/SERTAD3 轴抑制乳腺癌细胞的生长和对 TAM 的抗性

摘要

长链非编码 RNA (lncRNA) 可以对癌细胞的耐药性产生影响。本研究调查了 lncRNA HNF1A-反义 1 (HNF1A-AS1) 在乳腺癌 (BC) 细胞生长和他莫昔芬 (TAM) 敏感性中的作用。HNF1A-AS1 在 BC 细胞和组织中的表达得到促进。构建具有 HNF1A-AS1 沉默的 BC 细胞以检测细胞增殖。构建具有HNF1A-AS1沉默的TAM抗性细胞系和具有过表达HNF1A-AS1的亲本细胞系以测量耐药性。沉默 HNF1A-AS1 会降低 BC 细胞的增殖和 TAM 抗性。找出了 HNF1A-AS1 的下游 microRNAs (miRs) 及其靶标,并确定了它们在 BC 细胞 TAM 抗性中的功能。HNF1A-AS1 海绵化 miR-363 以促进 SERTAD3 表达。miR-363 的下调或SERTAD3 的上调刺激了BC 细胞的TAM 抗性。调查结果体内实验中复制了体外。可以得出结论,沉默 HNF1A-AS1 通过 miR-363/SERTAD3 轴和 TGF-β/Smad 通路的失活抑制 BC 细胞的生长和对 TAM 的耐药性。

更新日期:2021-05-17
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