Fangmei An1, Xiongbo Wu1, Yunan Zhang1, Dayang Chen1, Yexin Lin1, Fang Wu2, Junli Ding2, Min Xia1, Qiang Zhan1. 1. Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China. 2. Department of Oncology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China.
Abstract
BACKGROUND: Previous studies have shown that miR-224 regulates the progression of liver cancer. The aim of this study was to investigate the underlying mechanisms. METHODS: The miR-224, p-STAT3 and SMAD4 expression levels were checked with tissue or/and serum samples of HCC patients by qRT-PCR or IHC methods. The regulatory role of IL-6 in p-STAT3 and SMAD4 was investigated by Western-blot. The targeted gene of miR-224 was verified by both Western-blot and luciferase reporter assay. Furthermore, the carcinogenesis of miR-224 in HCC was investigated by cell experiments in vitro and mouse xenograft model and in vivo imaging in vivo. RESULTS: It was found miR-224 was elevated in both tissue and serum of HCC patients. The p-STAT3 expression was higher but the SMAD4 was lower in the HCC tumor tissues. Moreover, IL-6 can induce the p-STAT3/STAT3 and miR-224 expression in HCC cells and STAT3 played the bridge role between IL-6 and miR-224. Target gene studies found miR-224 targeted the 3'UTR of SMAD4. Finally, the promoting roles of miR-224in the growth, proliferation, invasion and migration of HCC were discovered by in vitro and in vivo studies. CONCLUSION: It implies that miR-224 may potentially represent a new target for developing novel anti-HCC therapeutics.
BACKGROUND: Previous studies have shown that miR-224 regulates the progression of liver cancer. The aim of this study was to investigate the underlying mechanisms. METHODS: The miR-224, p-STAT3 and SMAD4 expression levels were checked with tissue or/and serum samples of HCC patients by qRT-PCR or IHC methods. The regulatory role of IL-6 in p-STAT3 and SMAD4 was investigated by Western-blot. The targeted gene of miR-224 was verified by both Western-blot and luciferase reporter assay. Furthermore, the carcinogenesis of miR-224 in HCC was investigated by cell experiments in vitro and mouse xenograft model and in vivo imaging in vivo. RESULTS: It was found miR-224 was elevated in both tissue and serum of HCC patients. The p-STAT3 expression was higher but the SMAD4 was lower in the HCC tumor tissues. Moreover, IL-6 can induce the p-STAT3/STAT3 and miR-224 expression in HCC cells and STAT3 played the bridge role between IL-6 and miR-224. Target gene studies found miR-224 targeted the 3'UTR of SMAD4. Finally, the promoting roles of miR-224in the growth, proliferation, invasion and migration of HCC were discovered by in vitro and in vivo studies. CONCLUSION: It implies that miR-224 may potentially represent a new target for developing novel anti-HCC therapeutics.
Authors: P Y Hernanda; K Chen; A M Das; K Sideras; W Wang; J Li; W Cao; S J A Bots; L L Kodach; R A de Man; J N M Ijzermans; H L A Janssen; A P Stubbs; D Sprengers; M J Bruno; H J Metselaar; T L M ten Hagen; J Kwekkeboom; M P Peppelenbosch; Q Pan Journal: Oncogene Date: 2014-12-22 Impact factor: 9.867
Authors: Fangmei An; Alexandru V Olaru; Esteban Mezey; Qing Xie; Ling Li; Klaus B Piontek; Florin M Selaru Journal: J Clin Med Date: 2015-08-26 Impact factor: 4.241