Zhong Guobin, Lin Yuansheng, Wang Xu, Wang Keqiong, Liu Jianlun, Wei Wei
Department of Breast Surgery, Guangxi Medical University Cancer Hospital, Nanning, People's Republic of China.
Department of Pharmacy, Guangxi Medical University Cancer Hospital, Nanning, People's Republic of China.
Onco Targets Ther. 2020 Dec 7;13:12501-12513. doi: 10.2147/OTT.S280142. eCollection 2020.
Breast cancer (BC) is the most common cancer in women. Emerging evidence has demonstrated that lncRNAs play an important role in BC. The objective of this study was to investigate the impact of the long non-coding RNA (lncRNA), H19/miRNA-130a-3P/special AT-rich sequence-binding protein-1 (SATB1) axis on BC progression.
Expression of lncRNA and RNA was quantified via RT-qPCR. CCK-8, colony formation, wound healing, transwell, and flow cytometric analyses were used to analyze the proliferation, migration, invasion and apoptosis of cells. A dual-luciferase reporter assay and a RNA immunoprecipitation (RIP) assay were used to assess molecular binding. Protein levels were measured by Western blotting. The function of the lncRNA H19 (hereafter referred to as H19) was examined by xenotransplantation.
We demonstrated that H19 expression was higher in cancer tissues and cancer cell lines than in adjacent non-tumor tissues and normal cell lines, respectively. H19 silencing inhibited the proliferation, migration and invasion of BC cells, and induced apoptosis. In addition, H19 directly bound to miR-130a-3p and downregulated its expression. We further demonstrated that H19 sponged miRNA-130a-3p, which resulted in SATB1 upregulation, thus promoting BC progression. Silencing of H19 substantially suppressed BC tumorigenesis in vivo.
Our data uncovered a novel mechanism of BC progression based on the H19-miR-130a-3p-SATB1 axis.
乳腺癌(BC)是女性中最常见的癌症。新出现的证据表明,长链非编码RNA(lncRNA)在乳腺癌中发挥着重要作用。本研究的目的是探讨长链非编码RNA(lncRNA)H19/微小RNA-130a-3P/富含特殊AT序列结合蛋白1(SATB1)轴对乳腺癌进展的影响。
通过逆转录定量聚合酶链反应(RT-qPCR)对lncRNA和RNA的表达进行定量。采用细胞计数试剂盒-8(CCK-8)、集落形成、伤口愈合、Transwell和流式细胞术分析来检测细胞的增殖、迁移、侵袭和凋亡。采用双荧光素酶报告基因检测和RNA免疫沉淀(RIP)检测来评估分子结合情况。通过蛋白质免疫印迹法检测蛋白质水平。通过异种移植实验研究lncRNA H19(以下简称H19)的功能。
我们发现,H19在癌组织和癌细胞系中的表达分别高于相邻非肿瘤组织和正常细胞系。H19沉默可抑制乳腺癌细胞的增殖、迁移和侵袭,并诱导细胞凋亡。此外,H19直接与miR-130a-3p结合并下调其表达。我们进一步证明,H19作为miR-130a-3p的海绵,导致SATB1上调,从而促进乳腺癌进展。H19沉默在体内显著抑制了乳腺癌的肿瘤发生。
我们的数据揭示了一种基于H19-miR-130a-3p-SATB1轴的乳腺癌进展新机制。