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微小RNA-199b-5p通过Scribble/Lgl靶向顶端-基底极性来抑制口腔鳞状细胞癌。

miRNA-199b-5p suppresses of oral squamous cell carcinoma by targeting apical-basolateral polarity via Scribble/Lgl.

作者信息

Kim Shihyun, Park Suyeon, Kim Yong-Jae, Hyun Jeongeun, Choi Jongho

机构信息

Department of Oral Pathology, College of Dentistry, Gangneung-Wonju National University, Gangneung-si, Gangwon-do 25457, Republic of Korea.

Department of Nanobiomedical Science & BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan-si, Chungcheongnam-do 31116, Republic of Korea.

出版信息

Mol Ther Nucleic Acids. 2024 Oct 18;35(4):102363. doi: 10.1016/j.omtn.2024.102363. eCollection 2024 Dec 10.

Abstract

In epithelial cells, Scribble forms cell-cell junctions and contributes to cell morphology and homeostasis by regulating apical-basolateral polarity in mammals and functions as a tumor suppressor in many carcinomas. The initial diagnosis of oral squamous cell carcinoma is important, and its prognosis is poor when accompanied by metastasis. However, research on the mechanisms of oral squamous cell carcinoma metastasis is insufficient. Herein, we showed that Scribble regulates the apical-basolateral polarity of oral squamous cell carcinoma by regulating lethal giant larvae 1, Scribble module and E-cadherin, the adhesion junction. The expression of lethal giant larvae 1 and E-cadherin decreased when the expression of Scribble was knocked down and their localization was completely disrupted in both the oral squamous cell carcinoma cell line and model. In particular, the Scribble was involved in oral squamous cell carcinoma metastasis via hsa-miR-199b-5p, which is a microenvironmental factor of hypoxia. The disruption of Scribble localization under hypoxic conditions, but its localization was maintained in miR-199b-5p oral squamous cell carcinoma cell lines and . These results suggest that Scribble functions as a tumor suppressor marker mediated by miR-199b-5p in oral squamous cell carcinoma.

摘要

在上皮细胞中,Scribble形成细胞间连接,并通过调节哺乳动物的顶-基极性来维持细胞形态和内环境稳定,在许多癌症中发挥肿瘤抑制作用。口腔鳞状细胞癌的早期诊断很重要,伴有转移时预后较差。然而,关于口腔鳞状细胞癌转移机制的研究尚不充分。在此,我们发现Scribble通过调节致死性巨幼虫1、Scribble模块和黏附连接蛋白E-钙黏蛋白来调控口腔鳞状细胞癌的顶-基极性。敲低Scribble的表达后,致死性巨幼虫1和E-钙黏蛋白的表达降低,且在口腔鳞状细胞癌细胞系和模型中它们的定位完全被破坏。特别是,Scribble通过缺氧微环境因子hsa-miR-199b-5p参与口腔鳞状细胞癌转移。在缺氧条件下Scribble的定位被破坏,但在miR-199b-5p口腔鳞状细胞癌细胞系中其定位得以维持。这些结果表明,在口腔鳞状细胞癌中,Scribble作为由miR-199b-5p介导的肿瘤抑制标志物发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b79a/11570515/62f254da85a8/fx1.jpg

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