长链非编码RNA SATB2-AS1通过促进乳腺癌转移抑制因子1样蛋白来抑制微小RNA-155-3p，从而抑制乳腺癌细胞生长。
Long non-coding RNA SATB2-AS1 inhibits microRNA-155-3p to suppress breast cancer cell growth by promoting breast cancer metastasis suppressor 1-like.
作者信息
Cheng Shaoqiang, Xia Bingshu, Li Hongbin, Li Yuying, Lv Xinxin, Zhang Yue, Huang Yuanxi
机构信息
Department of Breast Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, China.
出版信息
Cancer Cell Int. 2020 Jul 17;20:321. doi: 10.1186/s12935-020-01411-8. eCollection 2020.
BACKGROUND
Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play vital roles in human cancers. Nevertheless, the effects of lncRNAs and miRNAs on breast cancer (BC) remain to be further investigated. This study was designed to testify the roles of lncRNA antisense transcript of SATB2 protein (SATB2-AS1) and microRNA-155-3p (miR-155-3p) in BC progression.
METHODS
Levels of SATB2-AS1, miR-155-3p and breast cancer metastasis suppressor 1-like (BRMS1L) in BC were determined. The prognostic role of SATB2-AS1 in BC patients was assessed. The screened cells were respectively introduced with altered SATB2-AS1 or miR-155-3p to figure out their roles in malignant phenotypes of BC cells. The effect of varied SATB2-AS1 and miR-155-3p on BC cells in vivo was observed. Dual luciferase reporter gene assay and RNA-pull down assay were implemented to detect the targeting relationship of SATB2-AS1, miR-155-3p, and BRMS1L.
RESULTS
SATB2-AS1 and BRMS1L were decreased while miR-155-3p was increased in BC cells and tissues. Patients with lower SATB2-AS1 expression had poor prognosis. Elevated SATB2-AS1 and inhibited miR-155-3p were able to restrain malignant behaviors of BC cells in vitro, as well as decelerate tumor growth in vivo. Oppositely, inhibited SATB2-AS1 and amplified miR-155-3p had converse effects on BC cell growth. MiR-155-3p mimic abrogated the impact of overexpressed SATB2-AS1. SATB2-AS1 could sponge miR-155-3p, and BRMS1L was the target gene of miR-155-3p.
CONCLUSION
Elevated SATB2-AS1 and inhibited miR-155-3p could suppress the malignant phenotypes of BC cells, thereby restricting the development of BC.
背景
长链非编码RNA（lncRNAs）和微小RNA（miRNAs）在人类癌症中发挥着至关重要的作用。然而，lncRNAs和miRNAs对乳腺癌（BC）的影响仍有待进一步研究。本研究旨在证实SATB2蛋白反义转录本lncRNA（SATB2-AS1）和微小RNA-155-3p（miR-155-3p）在BC进展中的作用。
方法
测定BC中SATB2-AS1、miR-155-3p和乳腺癌转移抑制因子1样蛋白（BRMS1L）的水平。评估SATB2-AS1在BC患者中的预后作用。分别将改变后的SATB2-AS1或miR-155-3p导入筛选出的细胞，以明确它们在BC细胞恶性表型中的作用。观察不同的SATB2-AS1和miR-155-3p对体内BC细胞的影响。采用双荧光素酶报告基因检测和RNA下拉实验检测SATB2-AS1、miR-155-3p和BRMS1L之间的靶向关系。
结果
在BC细胞和组织中，SATB2-AS1和BRMS1L水平降低，而miR-155-3p水平升高。SATB2-AS1表达较低的患者预后较差。升高SATB2-AS1并抑制miR-155-3p能够在体外抑制BC细胞的恶性行为，以及在体内减缓肿瘤生长。相反，抑制SATB2-AS1并增强miR-155-3p对BC细胞生长有相反的作用。miR-155-3p模拟物消除了过表达SATB2-AS1的影响。SATB2-AS1可以吸附miR-155-3p，且BRMS1L是miR-155-3p的靶基因。
结论
升高SATB2-AS1并抑制miR-155-3p可抑制BC细胞的恶性表型，从而限制BC的发展。
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