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The stability of FKBP9 maintained by BiP is crucial for glioma progression
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作者 Shirong Li Wangxiao Xia +10 位作者 Bin Sun Weiyan Peng Dong Yang Jing Gao Shuai He Hua Yang Yongjie Zhu Hu Zhou Tingxiu Xiang Qingpeng Kong Xudong Zhao 《Genes & Diseases》 SCIE CSCD 2024年第6期441-451,共11页
FK506-binding protein 9(FKBP9)is involved in tumor malignancy by resistance to endoplasmic reticulum(ER)stress,and the up-regulation of FKBP9 is associated with patients'poor prognosis.The current knowledge of the... FK506-binding protein 9(FKBP9)is involved in tumor malignancy by resistance to endoplasmic reticulum(ER)stress,and the up-regulation of FKBP9 is associated with patients'poor prognosis.The current knowledge of the molecular mechanisms is still limited.One pre-vious study showed that FKBP9 could confer glioblastoma cell resistance to ER stress through ASK1-p38 signaling.However,the upstream regulatory mechanism of FKBP9 expression is still indistinct.In this study,we identified the FKBP9 binding proteins using co-immunoprecipitation followed by mass spectrometry.Results showed that FKBP9 interacted with the binding immu-noglobulin protein(BiP).BiP bound directly to FKBP9 with high affinity.BiP prolonged the half-life of the FKBP9 protein and stabilized the FKBP9 protein.BiP and FKBP9 protein levels were positively correlated in patients with glioma,and patients with high expression of BiP and FKBP9 showed a worse prognosis.Further studies showed that FKBP9 knockout in genetically engineered mice inhibited intracranial glioblastoma formation and prolonged survival by decreasing cellular proliferation and ER stress-induced CHOP-related apoptosis.Moreover,normal cells may depend less on FKBP9,as shown by the absence of apoptosis upon FKBP9 knockdown in a non-transformed human cell line and overall normal development in homozygous knockout mice.These findings suggest an important role of BiP-regulated FKBP9-associated signaling in glioma progression and the BiP-FKBP9 axis may be a potential therapeutic target forglioma. 展开更多
关键词 BIP Endoplasmic reticulum stress FKBP9 GLIOMA Knockout mice
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Breast cancer development and progression:Risk factors,cancer stem cells,signaling pathways,genomics,and molecular pathogenesis 被引量:31
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作者 Yixiao Feng Mia Spezia +15 位作者 Shifeng Huang Chengfu Yuan Zongyue Zeng Linghuan Zhang Xiaojuan Ji Wei Liu Bo Huang Wenping Luo Bo Liu Yan Lei Scott Du Akhila Vuppalapati Hue H.Luu Rex C.Haydon Tong-Chuan He Guosheng Ren 《Genes & Diseases》 SCIE 2018年第2期77-106,共30页
As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous disea... As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast.While the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this malignancy.Breast cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in between.Within the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites.It is important to distinguish between the various subtypes because they have different prognoses and treatment implications.As there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem cells.Normal breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell motility.Furthermore,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast cancer.This review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer. 展开更多
关键词 BRCA1/2 Breast cancer Cancer stem cells Estrogen receptors HER2 Noncoding RNAs Triple-negative breast cancer Tumor heterogeneity
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Depression and stress levels increase risk of liver cancer through epigenetic downregulation of hypocretin 被引量:3
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作者 Chunyun Pu Shaorong Tian +9 位作者 Sanxiu He Weihong Chen Yuanyuan He Hongyan Ren Jing Zhu Jun Tang Xiaolan Huang Ying Xiang Yixiao Fu Tingxiu Xiang 《Genes & Diseases》 SCIE 2022年第4期1024-1037,共14页
Recent studies suggest that Hypocretin (HCRT, Orexin) are involved in stress regulation of depression through the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanism by which Hypocretin regulat... Recent studies suggest that Hypocretin (HCRT, Orexin) are involved in stress regulation of depression through the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanism by which Hypocretin regulate neurobiological responses is unknown. Herein, the effects of chronic stress on the epigenetic modification of HCRT and its association with depression were explored with regard to a potential role in cancer progression. In the study, Sprague Dawley (SD) rats were used to establish an animal model of cancer with depression by administrating n-nitrosodiethylamine (DEN) and chronic unpredictable mild stress (CUMS). RNA-sequencing was used to detect differentially expressed genes in the hippocampus of rats and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the results of RNA-sequencing. The status of HCRT promoter methylation was assessed by methylation specific polymerase chain reaction. Behavioral tests showed that rats exposed to CUMS had significant depressive-like behaviors. The number of liver tumors and tumor load in depressed rats exposed to CUMS was higher than in SD rats without CUMS. RNA-sequencing revealed that HCRT was one of the most siginificantly downregulated gene in the hippocampus of SD rats with CUMS compared to non-stressed group, which was validated by qRT-PCR. HCRT mRNA expression was downregulated and the promoter for HCRT was hyper-methylated in those with depression. These results identified a critical role for chronic psychological stressors in tumorigenesis and cancer progression, via epigenetic HCRT downregulation. Such epigenetic downregulation may be the molecular basis for the association of cancer with depression. 展开更多
关键词 Cancer Chronic unpredictability mild stress CpG methylation Depressi on HYPOCRETIN
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Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis 被引量:1
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作者 Yixiao Feng Mia Spezia +15 位作者 Shifeng Huang Chengfu Yuan Zongyue Zeng Linghuan Zhang Xiaojuan Ji Wei Liu Bo Huang Wenping Luo Bo Liu Yan Lei Scott Du Akhila Vuppalapati Hue H.Luu Rex C.Haydon Tong-Chuan He Guosheng Ren 《Genes & Diseases》 SCIE 2018年第3期77-106,共30页
As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous disea... As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global scale.Breast cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the breast.While the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this malignancy.Breast cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in between.Within the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor sites.It is important to distinguish between the various subtypes because they have different prognoses and treatment implications.As there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem cells.Normal breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell motility.Furthermore,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast cancer.This review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer. 展开更多
关键词 BRCA1/2 Breast cancer Cancer stem cells Estrogen receptors HER2 Noncoding RNAs Triple-negative breast cancer Tumor heterogeneity
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Zinc-finger protein 382 antagonises CDC25A and ZEB1 signaling pathway in breast cancer 被引量:2
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作者 Shuman Li Xiaoqian He +14 位作者 Yan Wang Weihong Chen Ran Sun Shaorong Tian Sanxiu He Chunyun Pu Chen Li Dishu Zhou Yu Jiang Qian Tao Lili Li Lin Ye Yue Wu Weiyan Peng Tingxiu Xiang 《Genes & Diseases》 SCIE CSCD 2023年第2期568-582,共15页
Our previous studies found that Zinc-finger protein 382(ZNF382)played as a tumor suppressor gene in esophageal and gastric cancers,and a positive correlation between the high expression of ZNF382 and better outcome in... Our previous studies found that Zinc-finger protein 382(ZNF382)played as a tumor suppressor gene in esophageal and gastric cancers,and a positive correlation between the high expression of ZNF382 and better outcome in breast cancer patients.However,the biological roles and mechanisms of ZNF382 in breast cancer remains unclear.We detected ZNF382 expression by reverse-transcription PCR(RT-PCR)and real-time quantitative PCR(qRT-PCR)in breast cancer cells and tissues,and explored the impacts and mechanisms of ectopic ZNF382 expression in breast cancer cells in vitro and in vivo,respectively.Our results revealed that ZNF382 was significantly down-regulated in breast cancer tissues compared with adjacent non-cancer tissues.Restoration of ZNF382 expression in silenced breast cancer cells not only inhibited tumor cell colony formation,viability,migration and invasion,and epithelial-mesenchymal-transition(EMT),but also induced apoptosis and G0/G1 arrest.In conclusion,ZNF382 could induce G0/G1 cell cycle arrest through inhibiting CDC25A signaling,and,inhibit cell migration,invasion and EMT by antagonizing ZEB1 signaling in breast cancer cells. 展开更多
关键词 Breast cancer CDC25A EMT ZEB1 ZNF382
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LPCAT1 functions as a novel prognostic molecular marker in hepatocellular carcinoma
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作者 Hongbin Zhang Ke Xu +15 位作者 Qin Xiang Lijuan Zhao Benxu Tan Ping Ju Xiufu Lan Yi Liu Jian Zhang Zheng Fu Chao Li Jinzhi Wang Jixiang Song Yun Xiao Zhaobo Cheng Yan Wang Shu Zhang Tingxiu Xiang 《Genes & Diseases》 SCIE 2022年第1期151-164,共14页
This study aimed to investigate the relationships between LPCAT1 expression and clinicopathologic parameters of hepatocellular carcinoma(HCC),further,to explore the effect of LPCAT1 on overall survival(OS)in patients ... This study aimed to investigate the relationships between LPCAT1 expression and clinicopathologic parameters of hepatocellular carcinoma(HCC),further,to explore the effect of LPCAT1 on overall survival(OS)in patients with HCC,and its possible mechanism.Bioinformatics analysis using high throughput RNA-sequencing data from TCGA was utilized to explore the differential expression of LPCAT1 between normal and tumor tissues,and the associations between LPCAT1 expression and clinicopathological parameters.Survival analyses and subgroup survival analyses were utilized to elucidate the effect of LPCAT1 on OS in patients with HCC.Univariate analysis and multivariate analysis were used to investigate the prognostic factors.Potential LPCAT1 related tumor genes were identified by the methodology of differentially expressed genes(DEGs)screening.GO term enrichment analysis,KEGG pathway analysis and the PPI network were used to explore the potential mechanism.LPCAT1 was significantly overexpressed in HCC tumor tissues compared with normal tissues.The LPCAT1 expression was related to tumor grade,ECOG score,AFP and TNM stage,with P values of 0.000,0.000,0.007 and 0.000,respectively.Multivariate analysis demonstrated that LPCAT1 expression was independently associated with OS,with an HR of 1.04(CI:1.01–1.06,P=0.003).The KEGG pathway enrichment analyses showed that overlapped DEGs mainly participate in the cell cycle.Finally,we identified a hub gene,CDK1,which has been reported to act on the cell cycle,consistent with the result of KEGG enrichment analysis.Collectively,these data confirmed LPCAT1 was upregulated in HCC,and was an independent predictor of the prognosis. 展开更多
关键词 CDK1 HCC LPCAT1 Overall survival Prognostic marker
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