Oral and Maxillofacial Surgery, Cangzhou Central Hospital, No. 16 Xinhua West Road, Cangzhou, Hebei 061000 People's Republic of China.
Cell Mol Biol Lett. 2018 Jun 18;23:28. doi: 10.1186/s11658-018-0094-0. eCollection 2018.
It has been reported that the expression of activating transcription factor 3 (ATF3) is closely associated with both microRNA (miRNA) processing and the progress of many cancers. Our study aimed to explore the interaction between ATF3 and miR-488 in tongue squamous cell carcinoma (TSCC).
Quantitative real-time PCR was performed to detect the levels of ATF3 and miR-488 in TSCC tissues and cell lines. Cell invasion and epithelial-mesenchymal transition (EMT) were assessed to determine the biological functions of miR-488 and ATF3 in TSCC cells. The mRNA and protein levels of ATF3 were measured using quantitative RT-PCR and western blotting. Luciferase assays were performed to validate ATF3 as an miR-488 target in TSCC cells.
We found that the level of miR-488 significantly decreased and the expression of ATF3 significantly increased in TSCC tissues and cell lines. A low level of miR-488 was closely associated with increased expression of ATF3 in TSCC tissues. Introducing miR-488 significantly inhibited the invasion and EMT of TSCC cells, and knockdown of miR-488 promoted both processes. The bioinformatics analysis predicted that ATF3 is a potential target gene of miR-488. The luciferase reporter assay showed that miR-488 could directly target ATF3. ATF3 silencing had similar effects to miR-488 overexpression on TSCC cells. Overexpression of ATF3 in TSCC cells partially reversed the inhibitory effects of the miR-488 mimic.
miR-488 inhibited cell invasion and EMT of TSCC cells by directly downregulating ATF3 expression.
已有报道称，激活转录因子 3（ATF3）的表达与 microRNA（miRNA）加工和多种癌症的进展密切相关。本研究旨在探讨 ATF3 与舌鳞状细胞癌（TSCC）中 miR-488 的相互作用。
采用实时定量 PCR 检测 TSCC 组织和细胞系中 ATF3 和 miR-488 的水平。通过细胞侵袭和上皮-间充质转化（EMT）评估来确定 miR-488 和 ATF3 在 TSCC 细胞中的生物学功能。采用定量 RT-PCR 和 Western blot 检测 ATF3 的 mRNA 和蛋白水平。通过荧光素酶报告基因实验验证 ATF3 是 TSCC 细胞中 miR-488 的靶基因。
我们发现，miR-488 的水平在 TSCC 组织和细胞系中显著降低，而 ATF3 的表达显著升高。在 TSCC 组织中，miR-488 水平低与 ATF3 表达增加密切相关。引入 miR-488 可显著抑制 TSCC 细胞的侵袭和 EMT，而 miR-488 的敲低则促进了这两个过程。生物信息学分析预测 ATF3 是 miR-488 的潜在靶基因。荧光素酶报告基因实验表明，miR-488 可以直接靶向 ATF3。ATF3 沉默对 TSCC 细胞的作用与 miR-488 过表达相似。在 TSCC 细胞中过表达 ATF3 部分逆转了 miR-488 模拟物的抑制作用。
miR-488 通过直接下调 ATF3 表达抑制 TSCC 细胞的侵袭和 EMT。
