title: Insulin-like growth factor 1 receptor (IGF-1R) as a target of MiR-497 and plasma IGF-1R levels associated with TNM stage of pancreatic cancer.
abstract: The expression levels and regulatory roles of miR-497 in pancreatic cancer are unclear. The clinical value of plasma insulin-like growth factor 1 receptor (IGF-1R) in pancreatic cancers has not been investigated. In the present study, we demonstrated that miR-497 was significantly downregulated in pancreatic cancer tissues. Upregulation of miR-497 in BxPC-3 and AsPC-1 pancreatic cancer cell lines inhibited proliferation, enhanced apoptosis, re-sensitized cells to gemcitabine and suppressed IGF-1R and p-AKT expression through direct downregulation of IGF-1R protein expression. Opposite effects were observed after downregulation of miR-497. Plasma IGF-1R levels in patients with pancreatic cancer increased significantly, compared with that in patients with chronic pancreatitis, other pancreatic tumors and pancreatic neuroendocrine tumors (P = 0.006, P = 0.018 and P = 0.004, respectively), and displayed potential values for distinguishing pancreatic lesions. However, the levels in pancreatic cancer patients were comparable to that in healthy volunteers (P = 0.095). The tumor locations and TNM stage were associated with plasma IGF-1R levels (P = 0.013 and P = 0.01, respectively). There was no significant difference of overall survival between high and low IGF-1R expression groups. In conclusion, we demonstrated that miR-497 attenuated the malignancy of pancreatic cancer cells and promoted sensitivity of cells to gemcitabine by directly downregulation of IGF-1R expression. Plasma IGF-1R displayed a potential value for distinguishing pancreatic lesions and could be a new biomarker for guiding TNM stage of pancreatic cancer.
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Xu
authors.affiliation: Department of Head and Neck Surgery, Beijing Cancer Hospital and Institute, Peking University Cancer Hospital, Beijing, China.
authors.forename: Tian-Xiao
authors.initials: TX
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: You
authors.affiliation: Department of Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Lian-Fang
authors.initials: LF
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Shu
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Tai-Ping
authors.initials: TP
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yu-Pei
authors.initials: YP
authors.lastname: Zhao
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000097:blood*; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D017526:Receptor, IGF Type 1 / Q000097:blood*; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D003841:Deoxycytidine; D017526:Receptor, IGF Type 1; D000093542:Gemcitabine