High CTCF expression mediated by FGD5-AS1/miR-19a-3p axis is associated with immunosuppression and pancreatic cancer progression
Yihao Liu,
Wenxin Qi,
Jingxin Yin,
Xirui He,
Songqi Duan,
Haili Bao,
Chen Li,
Minmin Shi,
Jiao Wang,
Shaohua Song
Affiliations
Yihao Liu
Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Pancreatic Neoplams Translational Medicine
Wenxin Qi
School of Life Sciences, Shanghai University, Shanghai, China
Jingxin Yin
Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Pancreatic Neoplams Translational Medicine
Xirui He
School of Life Sciences, Shanghai University, Shanghai, China
Songqi Duan
Department of Zoology, College of Life Science, Nankai University, Tianjin, 300071 China
Haili Bao
Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Pancreatic Neoplams Translational Medicine
Chen Li
Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Pancreatic Neoplams Translational Medicine
Minmin Shi
Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Pancreatic Neoplams Translational Medicine; Corresponding author.
Jiao Wang
School of Life Sciences, Shanghai University, Shanghai, China; Corresponding author.
Shaohua Song
Department of General Surgery, Pancreatic Disease Center, Research Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Shanghai Key Laboratory of Pancreatic Neoplams Translational Medicine; Corresponding author.
The most common reason for cancer-related death globally is predicted to be pancreatic cancer (PC), one of the deadliest cancers. The CCCTC-binding factor (CTCF) regulates the three-dimensional structure of chromatin, was reported to be highly regulated in various malignancies. However, the underlying biological functions and possible pathways via which CTCF promotes PC progression remain unclear. Herein, we examined the CTCF function in PC and discovered that CTCF expression in PC tissues was significantly raised compared to neighboring healthy tissues. Additionally, Kaplan-Meier survival analysis demonstrated a strong connection between elevated CTCF expression and poor patient prognosis. A study of the ROC curve (receiver operating characteristic) revealed an AUC value for CTCF of 0.968. Subsequent correlation analysis exhibited a strong relationship between immunosuppression and CTCF expression in PC. CTCF knockdown significantly inhibited the malignant biological process of PC in vitro and in vivo, suggesting that CTCF may be a potential PC treatment target. We also identified the FGD5 antisense RNA 1 (FGD5-AS1)/miR-19a-3p axis as a possible upstream mechanism for CTCF overexpression. In conclusion, our data suggest that ceRNA-mediated CTCF overexpression contributes to the suppression of anti-tumor immune responses in PC and could be a predictive biomarker and potential PC treatment target.
