MiR-302b Suppresses Tumor Metastasis by Targeting Frizzled 6 in OSCC

作者全名："Sun, S.; Wang, J.; Liu, J.; Yin, F.; Xin, C.; Zeng, X.; Li, J.; Chen, Q."

作者地址："[Sun, S.; Wang, J.; Liu, J.; Yin, F.; Xin, C.; Zeng, X.; Li, J.; Chen, Q.] Sichuan Univ, West China Hosp Stomatol, Res Unit Oral Carcinogenesis & Management, Natl Clin Res Ctr Oral Dis,Chinese Acad Med Sci,S, Chengdu, Sichuan, Peoples R China; [Liu, J.] Chongqing Med Univ, Stomatol Hosp, Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing, Peoples R China"

通信作者："Zeng, X; Li, J; Chen, Q (corresponding author), Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, State Key Lab Oral Dis, 14,3rd Sect Ren Min Nan Rd,14,Sec 3,Renminnan Rd, Chengdu 610041, Sichuan, Peoples R China."

来源：JOURNAL OF DENTAL RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000664214600011

JCR分区：Q1

影响因子：7.6

年份：2021

卷号：100

期号：7

开始页：739

结束页：745

文献类型：Article

关键词：oral squamous cell carcinoma; microRNA-302b; FZD6; invasion; migration; prognosis

摘要："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."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81872211, 81771081, 81672675, U19A2005, 8162106]; 111 Project of MOE China [B14038]; Graduate Student's Research and Innovation Fund of Sichuan University [2018YJSY018]"

基金资助正文："The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was supported by grants from the National Natural Science Foundation of China (grants 81872211, 81771081, 81672675, U19A2005, 8162106), the 111 Project of MOE China (grant B14038), and the Graduate Student's Research and Innovation Fund of Sichuan University (grant 2018YJSY018)."