Insulin-like growth factor 2 mRNA-binding protein 1 promotes cell proliferation via activation of AKT and is directly targeted by microRNA-494 in pancreatic cancer  

作　　者：Bai-Shun Wan Ming Cheng Ling Zhang 

机构地区：[1]Department of Hepatobiliary and Pancreatic Surgery,the Affiliated Cancer Hospital of Zhengzhou University,Zhengzhou 450008,Henan Province,China [2]Department of Information,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,Henan Province,China

出　　处：《World Journal of Gastroenterology》2019年第40期6063-6076,共14页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China,No.61802350

摘　　要：BACKGROUND Studies have shown that insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1)plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role of IGF2BP1 in pancreatic cancer.METHODS Expression levels of IGF2BP1 and microRNA-494(miR-494)were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot.The relationship between IGF2BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed.The effect and mechanism of IGF2BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo.Analyses were performed to explore underlying mechanisms of IGF2BP1 upregulation in pancreatic cancer and assays were carried out to verify the posttranscriptional regulation of IGF2BP1 by miR-494.RESULTS We found that IGF2BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients.We showed that downregulation of IGF2BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway.Mechanistically,we showed that the frequent upregulation of IGF2BP1 was attributed to the downregulation of miR-494 expression in pancreatic cancer.Furthermore,we discovered that reexpression of miR-494 could partially abrogate the oncogenic role of IGF2BP1.CONCLUSION Our results revealed that upregulated IGF2BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2BP1 is partly due to the silencing of miR-494.BACKGROUND Studies have shown that insulin-like growth factor 2 m RNA-binding protein 1(IGF2 BP1) plays critical roles in the genesis and development of human cancers.AIM To investigate the clinical significance and role of IGF2 BP1 in pancreatic cancer.METHODS Expression levels of IGF2 BP1 and micro RNA-494(mi R-494) were mined based on Gene Expression Omnibus datasets and validated in both clinical samples and cell lines by quantitative real-time polymerase chain reaction and Western blot.The relationship between IGF2 BP1 expression and clinicopathological factors of pancreatic cancer patients was analyzed. The effect and mechanism of IGF2 BP1 on pancreatic cancer cell proliferation were investigated in vitro and in vivo.Analyses were performed to explore underlying mechanisms of IGF2 BP1 upregulation in pancreatic cancer and assays were carried out to verify the posttranscriptional regulation of IGF2 BP1 by mi R-494.RESULTS We found that IGF2 BP1 was upregulated and associated with a poor prognosis in pancreatic cancer patients. We showed that downregulation of IGF2 BP1 inhibited pancreatic cancer cell growth in vitro and in vivo via the AKT signaling pathway.Mechanistically, we showed that the frequent upregulation of IGF2 BP1 was attributed to the downregulation of mi R-494 expression in pancreatic cancer.Furthermore, we discovered that reexpression of mi R-494 could partially abrogate the oncogenic role of IGF2 BP1.CONCLUSION Our results revealed that upregulated IGF2 BP1 promotes the proliferation of pancreatic cancer cells via the AKT signaling pathway and confirmed that the activation of IGF2 BP1 is partly due to the silencing of mi R-494.

关 键 词：PANCREATIC cancer INSULIN-LIKE growth factor 2 mRNA-binding protein 1 Proliferation MicroRNA-494 

分 类 号：R73[医药卫生—肿瘤]