State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079, China.
The Second Charity Hospital of Henan Province, Jiaozuo 454000, China.
Biochem Biophys Res Commun. 2014 Jun 6;448(3):308-14. doi: 10.1016/j.bbrc.2014.02.032. Epub 2014 Feb 13.
ADAM10, overexpressed in tongue squamous cell carcinoma (TSCC), has been well documented for its role in tumor progression and metastasis. In the present study, we evaluated the inhibition effect of microRNAs (miRNAs) on the TSCC and identified that miR-140-5p could directly targets ADAM10 and inhibits the invasion and migration of TSCC cells. LAMC1, HDAC7 and PAX6, clustered into migration-related genes, were validated to be direct targets of miR-140-5p, while IGF1R and PSEN1 were not responsible to the regulation. Most intriguingly, ERBB4 was upregulated by miR-140-5p even though the interaction between ERBB4 3'UTR and miR-140-5p existed simultaneously. Meanwhile, ADAM10 is involved in the "positive" regulation of ERBB4 and negative regulation of PAX6 by miR-140-5p. Taken together, our results suggest that miR-140-5p play a role in TSCC cell migration and invasion, and two brand new relationships between miRNA and its targets emerged: (1) ADAM10 is not just a direct target of miR-140-5p, the repressed ADAM10 also helps to enhance the effect of miR-140-5p to other target genes: ERBB4 and PAX6; (2) ERBB4 is "positively" regulated by miR-140-5p.
ADAM10 在舌鳞状细胞癌（TSCC）中过表达，其在肿瘤进展和转移中的作用已有充分的文献记载。在本研究中，我们评估了 microRNAs（miRNAs）对 TSCC 的抑制作用，并鉴定出 miR-140-5p 可直接靶向 ADAM10 并抑制 TSCC 细胞的侵袭和迁移。LAMC1、HDAC7 和 PAX6 聚类为迁移相关基因，被验证为 miR-140-5p 的直接靶基因，而 IGF1R 和 PSEN1 不受调节。最有趣的是，尽管 ERBB4 3'UTR 与 miR-140-5p 存在相互作用，但 miR-140-5p 可上调 ERBB4。同时，ADAM10 参与 miR-140-5p 对 ERBB4 的“正”调节和对 PAX6 的负调节。总之，我们的结果表明，miR-140-5p 在 TSCC 细胞迁移和侵袭中发挥作用，并且 miRNA 与其靶基因之间出现了两个全新的关系：（1）ADAM10 不仅是 miR-140-5p 的直接靶基因，受抑制的 ADAM10 还有助于增强 miR-140-5p 对其他靶基因：ERBB4 和 PAX6 的作用；（2）ERBB4 被 miR-140-5p“正向”调节。
