mir-329 restricts tumor growth by targeting grb2 in pancreatic cancer
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Xinjing Wang1,2,3,*, Xiongxiong Lu1,2,3,*, Tian Zhang1,2,3,*, Chenlei Wen1,2,3, Minmin Shi3, Xiaomei Tang1,2,3, Hao Chen1,2,3, Chenghong Peng1,2,3, Hongwei Li1, Yuan Fang1,2,3, Xiaxing Deng1,2,3 and Baiyong Shen1,2,3
1 Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2 Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
3 Shanghai Institute of Digestive Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
* These authors have contributed equally to this work.
Baiyong Shen, email:
Xiaxing Deng, email:
Yuan Fang, email:
Keywords: pancreatic cancer, miR-329, GRB2, apoptosis
Received: August 12, 2015 Accepted: February 05, 2016 Published: February 14, 2016
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.
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