Department of Pathology, Shanxi Provincial People's Hospital, Taiyuan, Shanxi Province, China.
Eur Rev Med Pharmacol Sci. 2021 Jul;25(14):4655-4667. doi: 10.26355/eurrev_202107_26376.
Long non-coding RNA (lncRNA), is essential for the development and progression of cancers. LncRNA regulates target gene expression by sponging the corresponding microRNA (miRNA) during tumorigenesis. This work aimed to explore the role of one lncRNA, ELFN1-AS1, in colorectal cancer (CRC) development and elucidate the pertinent signaling pathway.
First, we found that ELFN1-AS1 was highly abundant in the human CRC tissues and cell lines. Silence of ELFN1-AS1 expression reduced cell proliferation, colony formation, migration and invasion, while inducing apoptosis in vitro; moreover, knockdown of ELFN1-AS1 decreased the size and weight of tumor in vivo.
Luciferase reporter assay revealed that ELFN1-AS1 interacted with miR-1205 and suppressed its expression. In addition, miR-1205 could bind to the 3' untranslated region (3'-UTR) of Metastasis Associated Protein1 (MTA1) and inhibited ELFN1-AS1 expression. More importantly, overexpression of MTA1 completely rescued the phenotype of ELFN1-AS1 knockdown.
In sum, our study demonstrated that ELFN1-AS1 sponges miR-1205 to upregulate MTA1, which is essential for CRC cell proliferation, migration, and invasion as well as apoptosis induction.
长链非编码 RNA(lncRNA)是癌症发生和发展的关键。在肿瘤发生过程中,lncRNA 通过海绵吸附相应的 microRNA(miRNA)来调节靶基因的表达。本研究旨在探讨 lncRNA ELFN1-AS1 在结直肠癌(CRC)发展中的作用,并阐明相关信号通路。
首先,我们发现 ELFN1-AS1 在人 CRC 组织和细胞系中高度丰富。ELFN1-AS1 表达沉默可降低细胞增殖、集落形成、迁移和侵袭能力,同时诱导体外细胞凋亡;此外,ELFN1-AS1 敲低可减小体内肿瘤的大小和重量。
荧光素酶报告基因检测显示,ELFN1-AS1 与 miR-1205 相互作用并抑制其表达。此外,miR-1205 可结合 Metastasis Associated Protein1(MTA1)的 3'非翻译区(3'-UTR)并抑制 ELFN1-AS1 的表达。更重要的是,MTA1 的过表达可完全挽救 ELFN1-AS1 敲低的表型。
综上所述,我们的研究表明,ELFN1-AS1 通过海绵吸附 miR-1205 而上调 MTA1,MTA1 对于 CRC 细胞的增殖、迁移和侵袭以及凋亡诱导至关重要。