Department of Oral and Maxillofacial Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Mol Cell Biochem. 2021 Feb;476(2):785-796. doi: 10.1007/s11010-020-03944-y. Epub 2020 Oct 22.
Growing evidence indicates that the non-coding 3'-untranslated region (3'UTR) of genes acts as competing endogenous RNAs (ceRNAs) to exert their roles in a number of diseases, including cancer. In the present study, MMP1 messenger RNA was identified to be significantly up-regulated in oral squamous cell carcinoma (OSCC) tissues, and both MMP1 and its 3'UTR promoted tumor growth and cell motility. Further mechanism investigations indicated that MMP1 3'UTR was able to antagonize miR-188-5p; in addition, overexpression of MMP1 3'UTR up-regulated the expression level of SOX4 and CDK4, target genes of miR-188-5p, which have also been identified as oncogenic driver genes in OSCC. Therefore, a ceRNA regulatory network among MMP1, SOX4, and CDK4 mediated via competing for binding to miR-188-5p was proved. Taken together, the present study demonstrates for the first time that MMP1 mRNA participates in the development of OSCC via ceRNA regulatory mechanism and genes involved in the ceRNA network may provide a novel avenue for target therapy.
越来越多的证据表明,基因的非编码 3'非翻译区(3'UTR)可作为竞争内源性 RNA(ceRNA)发挥作用,参与多种疾病的发生,包括癌症。本研究发现,基质金属蛋白酶 1(MMP1)信使 RNA 在口腔鳞状细胞癌(OSCC)组织中显著上调,MMP1 及其 3'UTR 均促进肿瘤生长和细胞迁移。进一步的机制研究表明,MMP1 3'UTR 能够拮抗 miR-188-5p;此外,MMP1 3'UTR 的过表达上调了 miR-188-5p 的靶基因 SOX4 和 CDK4 的表达水平,SOX4 和 CDK4 也被鉴定为 OSCC 的致癌驱动基因。因此,证明了 MMP1、SOX4 和 CDK4 之间通过竞争性结合 miR-188-5p 形成 ceRNA 调控网络。综上所述,本研究首次证明 MMP1 mRNA 通过 ceRNA 调控机制参与 OSCC 的发生,ceRNA 网络中的基因可能为靶向治疗提供新的途径。