State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China.
J Dent Res. 2021 Jul;100(7):739-745. doi: 10.1177/0022034520986551. Epub 2021 Jan 21.
Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of malignant epithelial tumors of the oral and maxillofacial region. OSCC has high rate of metastasis and poor prognosis. Tobacco and/or alcohol consumption and human papillomavirus infection are relatively exact susceptibility factors for OSCC, but the specific process of oral mucosal carcinogenesis and progression is very complicated. microRNA-302b (miR-302b) could regulate various characteristics of many tumor cells, such as proliferation and apoptosis, but its role and mechanism in OSCC have not been reported. This research aims to study the effect of miR-302b on the invasion and migration ability of OSCC and the mechanism by which it functions as well as to identify new prognostic indicators and therapeutic targets for OSCC patients. Functional studies showed that the miR-302b level was negatively correlated with the invasion and migration ability of OSCC. The studies also showed that the overexpression of miR-302b could attenuate the invasion and migration ability of OSCC cells and reduce lymphangiogenesis and the lung metastasis rate of OSCC cells in a mouse model. Mechanistic studies were performed by quantitative polymerase chain reactions, luciferase assays, and RNA pull-down experiments. The results verified that frizzled class receptor 6 (FZD6) is a target gene of miR-302b in OSCC that could promote cell invasion and migration. Clinical studies demonstrate that the protein expression level of FZD6 was higher in OSCC and metastatic lymph nodes than in normal oral mucosa epithelium. Taken together, these data showed that miR-302b could inhibit the invasion and migration ability of OSCC cells by targeting and downregulating FZD6, thereby inhibiting OSCC metastasis. As a new target gene of miR-302b, FZD6 has the potential to become a prognostic and therapeutic target for OSCC patients.
口腔鳞状细胞癌（OSCC）约占口腔颌面部恶性上皮肿瘤的 90%。OSCC 转移率高，预后差。烟草和/或酒精消费和人乳头瘤病毒感染是 OSCC 的相对明确的易感因素，但口腔黏膜癌变和进展的具体过程非常复杂。microRNA-302b（miR-302b）可以调节许多肿瘤细胞的各种特征，如增殖和凋亡，但它在 OSCC 中的作用和机制尚未报道。本研究旨在研究 miR-302b 对 OSCC 侵袭和迁移能力的影响及其作用机制，并鉴定 OSCC 患者的新预后指标和治疗靶点。功能研究表明，miR-302b 水平与 OSCC 的侵袭和迁移能力呈负相关。研究还表明，miR-302b 的过表达可以减弱 OSCC 细胞的侵袭和迁移能力，并降低 OSCC 细胞在小鼠模型中的淋巴管生成和肺转移率。通过定量聚合酶链反应、荧光素酶测定和 RNA 下拉实验进行了机制研究。结果验证了卷曲受体 6（FZD6）是 OSCC 中 miR-302b 的靶基因，可促进细胞侵袭和迁移。临床研究表明，FZD6 蛋白在 OSCC 和转移性淋巴结中的表达水平高于正常口腔黏膜上皮。综上所述，这些数据表明，miR-302b 通过靶向和下调 FZD6 抑制 OSCC 细胞的侵袭和迁移能力，从而抑制 OSCC 转移。作为 miR-302b 的新靶基因，FZD6 有可能成为 OSCC 患者的预后和治疗靶点。
