单位：[1]Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China[2]Department of Biliary-Pancreatic Surgery,Affiliated Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,Hubei Province,China.外科学系胆胰外科[3]Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.胆胰外科外科学系[4]Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China.
Background: By regulating target genes, microRNAs play essential roles in carcinogenesis and drug resistance in human pancreatic ductal adenocarcinoma (PDAC). Previous studies have shown that microRNA-10a-5p (miR-10a-5p) is overexpressed in PDAC and acts as an oncogene to promote the metastatic behavior of PDAC cells. However, the role of miR-10a-5p in PDAC chemoresistance remains unclear. Methods: The effects of miR-10a-5p on biological behaviors were analyzed. MiR-10a-5p and TFAP2C levels in tissues were detected, and the clinical value was evaluated. Results: We found that miR-10a-5p is up-regulated in gemcitabine-resistant PDAC cells and enhances PDAC cell gemcitabine resistance in vitro and vivo. Meanwhile, we also determined that miR-10a-5p promotes the migratory and invasive ability of PDAC cells. Next, we confirmed that transcription factor activating protein 2 gamma (TFAP2C) is a target of miR-10a-5p, and TFAP2C overexpression resensitizes PDAC cells to gemcitabine, which is initiated by miR-10a-5p. Further studies revealed that TFAP2C also decreased PDAC cell migration and invasion capability. Finally, survival analysis demonstrated that high miR-10a-5p expression levels and low TFAP2C expression levels were both independent adverse prognostic factors in patients with PDAC. Conclusion: Together, these results indicate that miR-10a-5p/TFAP2C may be new therapeutic target and prognostic marker in PDAC.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81472327, 81772639]; Major State Basic Research Development Program of China (973 Program)National Basic Research Program of China [2014CB542300]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001]; CAMS Central Public Welfare Research Institutes Fund for Basic science
第一作者单位：[1]Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Wangfujing Street, Beijing 100730, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Xiong Guangbing,Huang Hua,Feng Mengyu,et al.MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma[J].JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH.2018,37:doi:10.1186/s13046-018-0739-x.
APA：
Xiong, Guangbing,Huang, Hua,Feng, Mengyu,Yang, Gang,Zheng, Suli...&Zhao, Yupei.(2018).MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma.JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH,37,
MLA：
Xiong, Guangbing,et al."MiR-10a-5p targets TFAP2C to promote gemcitabine resistance in pancreatic ductal adenocarcinoma".JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH 37.(2018)
医学