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Down-regulated lncRNA SBF2-AS1 inhibits tumorigenesis and progression of breast cancer by sponging microRNA-143 and repressing RRS1.
Journal of Experimental & Clinical Cancer Research ( IF 11.4 ) Pub Date : 2020-01-17 , DOI: 10.1186/s13046-020-1520-5
Wenfei Xia 1 , Yun Liu 2 , Teng Cheng 1 , Tao Xu 1 , Menglu Dong 1 , Xiaopeng Hu 1
Affiliation  

BACKGROUND Recently, the roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in human diseases have been unveiled, this research was conducted to explore the impacts of lncRNA SET-binding factor 2-antisense RNA1 (SBF2-AS1), miR-143 and resistance to ralstonia solanacearum 1 (RRS1) on breast cancer (BC) development. METHODS The expression of SBF2-AS1, miR-143 and RRS1 in BC tissues, as well as in MDA-MB-231 and MCF-7 cell lines were assessed. Subsequently, the cells were transfected with miR-143 mimics or/and silenced or overexpressed SBF2-AS1 plasmids, and their negative controls. Then the proliferation, colony formation ability, cell cycle arrest, apoptosis, invasion and migration of the cells were assessed through gain- and loss-of-function experiments. Furthermore, the tumor growth, ki-67 expression and apoptosis in vivo were observed by subcutaneous tumorigenesis in nude mice. Binding relation between SBF2-AS1 and miR-143, and that between miR-143 and RRS1 were confirmed. RESULTS SBF2-AS1 and RRS1 were amplified, while miR-143 was reduced in BC tissues and cells. Reduced SBF2-AS1 and elevated miR-143 could repress the proliferation, invasion and migration via restraining RRS1 expression. Moreover, knockdown of SBF2-AS1 up-regulated miR-143 to promote the apoptosis of BC cells by downregulating RRS1, resulting in a prohibitive effect on the tumorigenesis and progression of BC. Results of in vivo experiments indicated that the inhibited SBF2-AS1 and overexpressed miR-143 could restrict BC cell proliferation and promote apoptosis, and decelerate tumor growth in xenografts. CONCLUSION We have discovered in this study that down-regulated SBF2-AS1 could inhibit tumorigenesis and progression of BC by up-regulation miR-143 and repressing RRS1, which provides basic therapeutic considerations for a novel target against BC.

中文翻译:

下调的lncRNA SBF2-AS1通过使microRNA-143海绵化并抑制RRS1抑制乳腺癌的发生和发展。

背景技术最近,人们揭示了长非编码RNA(lncRNA)和microRNA(miRNA)在人类疾病中的作用,该研究旨在探讨lncRNA SET结合因子2-反义RNA1(SBF2-AS1)的影响, miR-143和对乳腺癌(BC)发育的青枯雷尔氏菌1(RRS1)的抵抗力。方法评估SBF2-AS1,miR-143和RRS1在BC组织以及MDA-MB-231和MCF-7细胞系中的表达。随后,将细胞用miR-143模拟物或/和沉默或过表达的SBF2-AS1质粒及其阴性对照转染。然后通过获得和丧失功能的实验评估细胞的增殖,集落形成能力,细胞周期停滞,凋亡,侵袭和迁移。而且,肿瘤生长 通过皮下肿瘤发生在裸鼠中观察到ki-67在体内的表达和凋亡。证实了SBF2-AS1和miR-143之间的结合关系,以及miR-143和RRS1之间的结合关系。结果SBF2-AS1和RRS1被扩增,而miR-143在BC组织和细胞中减少。SBF2-AS1减少和miR-143升高可以通过抑制RRS1表达来抑制增殖,侵袭和迁移。此外,SBF2-AS1的敲低通过上调RRS1来上调miR-143以促进BC细胞的凋亡,从而对BC的肿瘤发生和发展产生抑制作用。体内实验结果表明,抑制的SBF2-AS1和过表达的miR-143可以限制BC细胞增殖并促进细胞凋亡,并降低异种移植物中的肿瘤生长。
更新日期:2020-01-17
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