p53 downregulates PD-L1 expression via miR-34a to inhibit the growth of triple-negative breast cancer cells: a potential clinical immunotherapeutic target

作者全名："Deng, Siyu; Wang, Mengna; Wang, Chenglong; Zeng, Yan; Qin, Xue; Tan, Yiwen; Liang, Bing; Cao, Youde"

作者地址："[Deng, Siyu; Wang, Mengna; Wang, Chenglong; Zeng, Yan; Qin, Xue; Liang, Bing; Cao, Youde] Chongqing Med Univ, Coll Basic Med, Dept Pathol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Wang, Chenglong] Chongqing Tradit Chinese Med Hosp, Dept Pathol, 6 Panxi Seventh Branch Rd, Chongqing 400021, Peoples R China; [Tan, Yiwen] Chongqing Med Univ, Dept Pathol, Affiliated Hosp 2, Chongqing 400010, Peoples R China; [Cao, Youde] Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Liang, B; Cao, YD (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Pathol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Cao, YD (通讯作者)，Chongqing Med Univ, Mol Med Diagnost & Testing Ctr, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：MOLECULAR BIOLOGY REPORTS

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000882563600001

JCR分区：Q3

影响因子：2.8

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Triple-negative breast cancer; p53; PD-L1; miR-34a

摘要："Background Compared with other breast cancer subtypes, triple-negative breast cancer (TNBC) has poorer responses to therapy and lower overall survival rates. The use of an inhibitor of immune checkpoint programmed cell death ligand 1 (PD-L1) is a promising treatment strategy and is approved for malignant tumors, especially for TNBC. p53 regulates various biological processes, but the association between p53 and immune evasion remains unknown. miR-34a is a known tumor suppressor and p53-regulated miRNA that is downregulated in several cancers; however, it has not been reported in TNBC. Herein, we aimed to explore the regulatory signaling axis among p53, miR-34a and PD-L1 in TNBC cells in vivo and in tissue and to improve our understanding of immunotherapy for TNBC. Methods and results p53-EGFP, p53-siRNA and miR-34a mimics were transfected into TNBC cell lines, and the interaction between miR-34a and PD-L1 was analyzed via dual-luciferase reporter assays. We found that p53 could inhibit the expression of PD-L1 via miR-34a and that miR-34a could inhibit both cell activity and migration and promoted apoptosis and cytotoxicity in TNBC. Furthermore, miR-34a agomir was injected into MDA-MB-231 tumors of nude mice. The results showed that miR-34a could inhibit tumor growth and downregulate the expression of PD-L1 in vivo. A total of 133 TNBC tissue samples were analyzed by immunochemistry; the proportion of positive expression of PD-L1 was 57.14% (76/133), and the proportion of samples with negative expression of PD-L1 was 42.86% (57/133). Conclusion Our research may provide a novel potential target for TNBC."

基金机构：National Natural Science Foundation of China [82102909]

基金资助正文：This work was supported by the National Natural Science Foundation of China (No. 82102909).