title: mir-329 restricts tumor growth by targeting grb2 in pancreatic cancer.
abstract: Pancreatic cancer is one of the most lethal malignancies worldwide. To illustrate the pathogenic mechanism(s), we looked into the expression and function of miR-329 associated with pancreatic cancer development. It was found that miR-329 expression was downregulated in the pancreatic cancer patients who demonstrated significantly shorter overall survival than the patients having upregulated expression. Also, more advanced pT stage cases were observed in the low miR-329 expression group of patients. Interestingly, our studies uncovered that miR-329 overexpression inhibited proliferation and induced apoptosis of pancreatic cancer cells, in contrast the miR-329 inhibitor reversed this phenomenon dramatically. Additionally, overexpression of miR-329 significantly limited tumor growth in the xenograft model. In the mechanistic study, we identified GRB2 as a direct target of miR-329 in pancreatic cancer cells, and expression of GRB2 was inversely correlated with miR-329 expression in pancreatic cancer patients. Furthermore, GRB2 overexpression in cell line and xenograft model dramatically diminished miR-329 mediated anti-proliferation and apoptosis induction, indicating that GRB2/pERK pathway was mainly downregulated by miR-329 expression. In general, our study has shed light on miR-329 regulated mechanism and, miR-329/GRB2/pERK is potential to be targeted for pancreatic cancer management.
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xinjing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiongxiong
authors.initials: X
authors.lastname: Lu
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Chenlei
authors.initials: C
authors.lastname: Wen
authors.affiliation: Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Minmin
authors.initials: M
authors.lastname: Shi
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Tang
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Chenghong
authors.initials: C
authors.lastname: Peng
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xiaxing
authors.initials: X
authors.lastname: Deng
authors.affiliation: Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.|Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Baiyong
authors.initials: B
authors.lastname: Shen
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D051380:GRB2 Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C584396:MIRN329 microRNA, human; D035683:MicroRNAs
keywords: GRB2; apoptosis; miR-329; pancreatic cancer