分类： 医学、药学 >> 基础医学 提交时间： 2023-09-28
Chang, Zhengyao
Li, Jiyang
Zhang, Chao
Gao, Yunhe
Liang, Wenquan
Pan, Heng
Zhang, Kecheng
Cui, Jianxin
Wei, Bo
Chen,Lin
Xi,Hongqing
摘要：Objective: Liver metastasis is one of the major causes of cancer-related death in gastric cancer (GC) patients. This study was to investigate the roles of THBS2 in the tumorigenesis and liver metastasis of GC and the sensitivity of GC to trastuzumab.
Methods: Sequencing was employed to identify the differentially expressed genes in the GC. The THBS2 expression was detected in GC tissues and GC cell lines, its relationships with clinicopathological characteristics were further assessed, and its roles in the malignant behaviors of GC were further investigated in vitro and in vivo, by up-regulating or down-regulating THBS2 expression. The PTEN and its downstream AKT and FAK signaling pathways were investigated in the GC aiming to explore the potential mechanism underlying the regulatory effects of THBS2.
Results: THBS2 expression increased significantly in the GC as compared to the normal gastric tissues, which was related to the distal metastasis and poor prognosis of GC patients. THBS2 expression also increased in the primary GC cells and human gastric cell line NCI-N87. THBS2 downregulation induced mesenchymal-epithelial transition (MET) and PTEN nuclear translocation, which inhibited the metastasis of GC cells. Carmofur promoted PTEN nuclear translocation, inhibiting the metastases and THBS2 downregulation together with carmofur improved the sensitivity of GC to trastuzumab.
Conclusions: THBS2 is overexpressed in GC tissues of patients with synchronous liver metastases and its overexpression is associated with poor prognosis. THBS2 downregulation inhibits the metastases of GC. THBS2 down-regulation and carmofur can be used as a new treatment for the advanced GC with metastases.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Chen, Jizheng
Guo, Min
Tang, Hong
Chen, Xinwen
Wang, Ning
Dong, Mei
Li, Zhong
Han, Xiao
Wang, Qian
Zhao, Yang
Zhuo, Zhiyong
Zhang, Chao
Chi, Xiumei
Pan, Yu
Jiang, Jing
Niu, Junqi
Yang, Dongliang
摘要：Class Ila histone deacetylases (HDACs), such as HDAC4, HDAC5, and HDAC7, provide critical mechanisms for regulating glucose homeostasis. Here we report that HDAC9, another class Ila HDAC, regulates hepatic gluconeogenesis via deacetylation of a Forkhead box 0 (FoxO) family transcription factor, FoxO1, together with HDAC3. Specifically, HDAC9 expression can be strongly induced upon hepatitis C virus (HCV) infection. HCV-induced HDAC9 upregulation enhances gluconeogenesis by promoting the expression of gluconeogenic genes, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, indicating a major role for HDAC9 in the development of HCV-associated exaggerated gluconeogenic responses. Moreover, HDAC9 expression levels and gluconeogenic activities were elevated in livers from HCV-infected patients and persistent HCV-infected mice, emphasizing the clinical relevance of these results. Our results suggest HDAC9 is involved in glucose metabolism, HCV-induced abnormal glucose homeostasis, and type 2 diabetes.
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