MicroRNA-301a promotes pancreatic cancer invasion and metastasis through the JAK/STAT3 signaling pathway by targeting SOCS5

被引:52
|
作者
Hu, Hui [1 ]
Zhang, Qin [1 ,2 ]
Chen, Weiqun [1 ,3 ,4 ]
Wu, Tangwei [1 ]
Liu, Shuiyi [1 ,3 ]
Li, Xiaoyi [1 ]
Luo, Bo [5 ]
Zhang, Tianzhu [1 ,2 ]
Yan, Ge [1 ,2 ]
Lu, Hongda [3 ,6 ]
Lu, Zhongxin [1 ,2 ,3 ,4 ]
机构
[1] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Med Lab, Wuhan 430014, Peoples R China
[2] Hubei Univ Chinese Med, Sch Lab Med, Wuhan 430065, Peoples R China
[3] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Canc Res Inst Wuhan, Wuhan 430014, Peoples R China
[4] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Key Lab Mol Diag Hubei Prov, Wuhan 430014, Peoples R China
[5] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Pathol, Wuhan 430014, Peoples R China
[6] Huazhong Univ Sci & Technol, Cent Hosp Wuhan, Tongji Med Coll, Dept Oncol, Wuhan 430014, Peoples R China
关键词
CELL-PROLIFERATION; PROGRESSION; EXPRESSION; PROTEINS; IMMUNITY;
D O I
10.1093/carcin/bgz121
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Pancreatic cancer is one of the most lethal digestive malignant tumors. We had previously found that microRNA-301a (miR-301a) is a oncogenic microRNA whose recognized conduce to nuclear factor-kappa B (NF-kappa B) activation in pancreatic cancer, yet the underlying mechanisms of miR-301a in promoting pancreatic cancer invasion and migration is obscure. In this work we found that high expression of miR-301a in human pancreatic cancer patients is related to poor survival. Overexpression of miR-301a enhances pancreatic cancer cell invasion, angiogenesis and migration, whereas inhibition of miR-301a suppresses pancreatic cancer cell invasion and reduces orthotopic pancreatic tumor growth and metastasis. Furthermore, suppressor of cytokine signaling 5 (SOCS5) is identified as a target gene of miR-301a. We found that miR-301a suppressed the expression of SOCS5 leads to janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) activation and is related to poor overall survival of pancreatic cancer patients. Taken together, our data show for the first time that the feedback loop between miR-301a and JAK/STAT3 pathway may play a significant role in pancreatic cancer invasion and metastasis. Targeting the loop may prove beneficial to prevent metastasis and provide a more effective therapeutic strategy for pancreatic cancer.
引用
收藏
页码:502 / 514
页数:13
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