School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan.
J Formos Med Assoc. 2021 Apr;120(4):1137-1142. doi: 10.1016/j.jfma.2020.09.006. Epub 2020 Oct 2.
BACKGROUND/PURPOSE: Oral cancer stem cells (CSCs) have been considered as the key cells that are implicated in tumor recurrence and metastasis. In recent years, great attention has been paid to the significance of various non-coding RNAs due to their regulatory roles in oral CSCs. Although the function of long non-coding RNA MEG3 in various cancers has been investigated, its effects on the features of oral CSCs remained to be determined.
The expression levels of MEG3 in tongue squamous cell carcinomas and prognostic effect have been evaluated. We assessed the expression of MEG3 in sphere cells (oral CSCs) using qRT-PCR. Secondary sphere formation and invasion assays were conducted to evaluate the self-renewal and metastatic abilities, respectively. Bioinformatics software and luciferase reporter assay were used to predict and verify the relationship between MEG3 and miR-421.
MEG3 was downregulated in the tissues of oral cancer and associated with a poor prognosis. In oral CSCs, the expression of MEG3 was repressed and overexpression of MEG3 resulted in suppression of self-renewal and invasion abilities. Luciferase reporter assay showed that miR-421 directly interacted with MEG3, and our subsequent experiment demonstrated that elevation of miR-421 reversed the MEG3-inhibited characteristics of oral CSCs.
Our findings suggest that MEG3 can serve as a tumor suppressor in oral CSCs by impeding the action of miR-421. Moreover, targeting MEG3-miR-421 axis has the potential to mitigate the tumor recurrence and metastasis.
背景/目的：口腔癌干细胞（CSCs）被认为是与肿瘤复发和转移有关的关键细胞。近年来，由于各种非编码 RNA 在口腔 CSCs 中的调控作用，它们的重要性受到了极大的关注。尽管长链非编码 RNA MEG3 在各种癌症中的功能已经得到了研究，但它对口腔 CSCs 特征的影响仍有待确定。
评估了 MEG3 在舌鳞癌细胞中的表达水平及其预后意义。我们使用 qRT-PCR 评估了 MEG3 在球体细胞（口腔 CSCs）中的表达。次级球体形成和侵袭实验分别用于评估自我更新和转移能力。生物信息学软件和荧光素酶报告实验用于预测和验证 MEG3 与 miR-421 之间的关系。
MEG3 在口腔癌组织中下调，与预后不良相关。在口腔 CSCs 中，MEG3 的表达受到抑制，过表达 MEG3 导致自我更新和侵袭能力受到抑制。荧光素酶报告实验表明，miR-421 可直接与 MEG3 相互作用，我们随后的实验表明，miR-421 的升高可逆转 MEG3 对口腔 CSCs 的抑制特征。
我们的研究结果表明，MEG3 可以通过抑制 miR-421 的作用在口腔 CSCs 中发挥肿瘤抑制作用。此外，靶向 MEG3-miR-421 轴有可能减轻肿瘤复发和转移。
