Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-gamma/JAK/STAT-1

作者全名："Wang, Shimeng; Wang, Xiangjian; Sun, Jun; Yang, Jin; Wu, Deyang; Wu, Fanglong; Zhou, Hongmei"

作者地址："[Wang, Shimeng; Wang, Xiangjian; Sun, Jun; Yang, Jin; Wu, Deyang; Wu, Fanglong; Zhou, Hongmei] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu, Peoples R China; [Wang, Shimeng; Wang, Xiangjian; Sun, Jun; Yang, Jin; Wu, Deyang; Wu, Fanglong; Zhou, Hongmei] Sichuan Univ, West China Hosp Stomatol, Natl Ctr Stomatol, Chengdu, Peoples R China; [Wang, Shimeng; Wang, Xiangjian; Sun, Jun; Yang, Jin; Wu, Deyang; Wu, Fanglong; Zhou, Hongmei] Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu, Peoples R China; [Wang, Shimeng; Wang, Xiangjian; Sun, Jun; Yang, Jin; Wu, Deyang; Wu, Fanglong; Zhou, Hongmei] Sichuan Univ, West China Hosp Stomatol, Frontier Innovat Ctr Dent Med Plus, Chengdu, Peoples R China; [Wang, Shimeng; Wang, Xiangjian; Sun, Jun; Yang, Jin; Wu, Deyang; Wu, Fanglong; Zhou, Hongmei] Sichuan Univ, West China Hosp Stomatol, Dept Oral Med, Chengdu, Peoples R China; [Wang, Xiangjian] Zhejiang Univ, Affiliated Hosp 2, Dept Oral Med, Sch Med, Hangzhou, Peoples R China; [Sun, Jun] Chongqing Med Univ, Stomatol Hosp, Dept Oral Med, Chongqing, Peoples R China"

通信作者："Wu, FL; Zhou, HM (通讯作者)，Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu, Peoples R China.; Wu, FL; Zhou, HM (通讯作者)，Sichuan Univ, West China Hosp Stomatol, Natl Ctr Stomatol, Chengdu, Peoples R China.; Wu, FL; Zhou, HM (通讯作者)，Sichuan Univ, West China Hosp Stomatol, Natl Clin Res Ctr Oral Dis, Chengdu, Peoples R China.; Wu, FL; Zhou, HM (通讯作者)，Sichuan Univ, West China Hosp Stomatol, Frontier Innovat Ctr Dent Med Plus, Chengdu, Peoples R China.; Wu, FL; Zhou, HM (通讯作者)，Sichuan Univ, West China Hosp Stomatol, Dept Oral Med, Chengdu, Peoples R China."

来源：INTERNATIONAL JOURNAL OF ORAL SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000974727400001

JCR分区：Q1

影响因子：10.8

年份：2023

卷号：15

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-gamma)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC."

基金机构："National Natural Science Foundation of China [82071124, 82002884, 82101028, 82102854]"

基金资助正文："AcknowledgementsThis study was supported by the National Natural Science Foundation of China (No. 82071124, 82002884, 82101028, 82102854)."