期刊：
JOURNAL OF CELLULAR PHYSIOLOGY,2021年236(5):3317-3335 ISSN：0021-9541
通讯作者：
Wen, Gebo;Zhong, Jing
作者机构：
[Wen, Gebo; Yang, Xinzhi; Zhong, Jing; Yang, Lu; Wen, GB; Zhong, J] Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.;[Wen, Gebo; Yang, Xinzhi; Zhong, Jing; Yang, Lu; Tan, Weihua] Univ South China, Affiliated Hosp 1, Inst Clin Med, Hengyang, Hunan, Peoples R China.;[Tan, Weihua] Univ South China, Affiliated Hosp 1, Emergency Dept, Hengyang, Hunan, Peoples R China.;[You, Yong; Wang, Jing] Univ South China, Hengyang Med Coll, Res Lab Translat Med, Hengyang, Hunan, Peoples R China.
通讯机构：
[Wen, GB; Zhong, J] U;Univ South China, Canc Res Inst, Hunan Prov Key Lab Tumor Cellular & Mol Pathol, Hengyang 421001, Hunan, Peoples R China.
关键词：
cancerous diseases;neoplastic diseases;protein sorting and trafficking;sorting nexins
摘要：
Sorting nexins (SNXs) are a diverse group of cytoplasmic- and membrane-associated phosphoinositide-binding proteins containing the PX domain proteins. The function of SNX proteins in regulating intracellular protein trafficking consists of endocytosis, endosomal sorting, and endosomal signaling. Dysfunctions of SNX proteins are demonstrated to be involved in several cancerous/neoplastic diseases. Here, we review the accumulated evidence of the molecular structure and biological function of SNX proteins and discuss the regulatory role of SNX proteins in distinct cancerous/neoplastic diseases. SNX family proteins may be a valuable potential biomarker and therapeutic strategy for diagnostics and treatment of cancerous/neoplastic diseases.
作者机构：
[Yao Yao; Zhong J.; Yang X.; Wang J.] Institute of Clinical Medicine, First Affiliated Hospital of University of South China, Hengyang, 421001, China;Department of Metabolism and Endocrinology, Second Affiliated Hospital of University of South China, Hengyang, 421001, China;[Dai X.] Department of General Surgery, Second Affiliated Hospital of University of South China, Hengyang, 421001, China;[Zhang Y.] Institute of Clinical Medicine, Second Affiliated Hospital of University of South China, Hengyang, 421001, China;Department of Metabolism and Endocrinology, First Affiliated Hospital of University of South China, Hengyang, 421001, China
通讯机构：
[Zhong, J.] I;Institute of Clinical Medicine, First Affiliated Hospital of University of South China, Hengyang, China
摘要：
Autophagy as a novel therapeutic target can inhibit or increase treatment efficacy in various types of breast cancer in a cell-type-dependent manner [1,2].Several studies have revealed that the coordination between Akt and the glycolytic pathway plays an indispensable role in mediating autophagy and caspase-dependent apoptosis,suggesting that a new regulatory mechanism for the process [3,4].Protein arginine N-methyltransferases(PRMTs)are eukaryotic enzymes that catalyze the transfer of methyl groups from S-adenosylmethionine to arginine residues of numerous PRMT substrates [5,6].PRMT2(also known as HRMT1L1)belongs to the arginine methyltransferase family [7].PRMT2β is a novel PRMT2 splice variant isolated from breast cancer cell [8].It occurs at the 3′ end of the PRMT2,resulting in loss of exons 7–9 and downstream frame-shifting [9].PRMT2β possesses 83 new amino acids at the C-terminus and its size is 301 amino acids.Our previous study reported that PRMT2β has potential antitumor effect by suppressing cyclin D1 expression [10].However,little is known about whether PRMT2β could regulate autophagy and glycolysis of MCF-7 cells.
期刊：
Molecular and Clinical Oncology,2017年7(6):935-942 ISSN：2049-9450
作者机构：
[Wen, Gebo; Zhong, Jing; Sun, Heng; Zu, Xuyu; Chen, Ling] Institute of Clinical Medicine, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China;[Wen, Gebo; Sun, Heng] Department of Metabolism and Endocrinology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China;[Zou, Jing] Department of Neurological Medicine, Hunan Institute of Gerontology, Hunan Geriatric Hospital, Changsha, Hunan 410016, P.R. China
关键词：
biological rationale;clinical issues;novel targeted therapies;obesity;prognosis;triple-negative breast cancer
摘要：
Triple-negative breast cancer (TNBC) is a subtype of breast cancer that lacks expression of the estrogen and progesterone receptor and does not overexpress human epidermal growth factor 2 receptor protein. TNBC is associated with special characteristics, including aggressiveness, poor prognosis and poor response to treatment, and has been attracting increasing attention worldwide. Obesity is a well-documented factor exerting a significant effect on the development of breast cancer, including TNBC. The purpose of the present review was to focus on the association between obesity and TNBC and provide a summary of novel research findings. The aim was to highlight the association between TNBC and obesity and provide an overview of novel outlooks on clinical issues, biological rationale, novel targeted therapies and prognosis, in order to draw attention to the significance of weight management, primary prevention, early diagnosis and treatment of this intractable disease.
关键词：
PRMT2 beta;antitumor;proliferation;breast cancer
摘要：
Our previous study reported several alternative splicing variants of arginine N-methyltransferase 2 (PRMT2), which lose different exons in the C-terminals of the wild-type PRMT2 gene. Particularly, due to frame-shifting, PRMT2 beta encodes a novel amino acid sequence at the C-terminus of the protein, the function of which is not understood. In the present study, we determined the role of PRMT2 beta in breast cancer cell proliferation, apoptosis and its effect on the Akt signaling pathway. Stable breast cancer MCF7 cell line with lentivirus-mediated PRMT2 beta overexpression was obtained after selection by puromycin for 2 weeks. The effect of lentivirus-mediated PRMT2 beta overexpression on breast cancer cellular oncogenic properties was evaluated by MTT, colony formation, cell cycle analysis and apoptosis assays in MCF7 cells. Luciferase activity assay and western blot analysis were performed to characterize the effects of PRMT2 beta on cyclin D1 promoter activities and the Akt signaling pathway. Tissue microarray was performed to investigate the association of PRMT2 beta with breast cancer progression. Lentivirus-mediated PRMT2 beta overexpression suppressed the cell proliferation and colony formation of breast cancer MCF7 cells. PRMT2 beta overexpression induced cell cycle arrest and apoptosis of MCF7 cells. Furthermore, PRMT2 beta was revealed to suppress the transcription activity of the cyclin D1 promoter, and PRMT2 beta was also found to inhibit cyclin D1 expression via the suppression of Akt/GSK-3 beta signaling in breast cancer cells. Clinically, it was revealed that PRMT2 beta expression was negatively correlated with human epidermal growth factor receptor 2 (HER2) (p=0.033) in breast tumors. Our results revealed that PRMT2 beta, a novel splice variant of PRMT2, plays potential antitumor effect by suppressing cyclin D1 expression and inhibiting Akt signaling activity. This also opens a new avenue for treating breast cancer.
关键词：
high mobility group A1;transforming growth factor-beta 1;breast cancer;human epidermal growth factor receptor 2
摘要：
Transforming growth factor-β1 (TGF-β1) signaling and high mobility group A (HMGA1) are known to play essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition. However, the correlation between TGF-β1 and HMGA1 in breast cancer cell is not yet well understood. In this study, we determined the effects of TGF-β1 on HMGA1 expression in breast cancer cells and examined the role of HMGA1 in breast cancer progression. Our results demonstrated that TGF-β1 induced the expression of HMGA1 in both MCF-7 and MDA-MB-231 breast cancer cells, as shown by RT-qPCR and immunofluorescence staining; however, the TGF-β1-induced expression of HMGA was blocked by treatment of the cells with phosphatidylinositol-3 kinase (PI3K) signaling inhibitors. Moreover, the HMGA1 promoter activity was found to be activated by TGF-β1 in the MCF-7 and MDA-MB-231 cells and we found that specificity protein 1 (Sp1) was involved in the TGF-β1-induced HMGA1 promoter activity, as shown by luciferase activity assay. Furthermore, the enforced expression of HMGA1 by transfection with a HMGA1 promoter enhanced cellular oncogenic properties, including proliferation, migration and invasion, and a tissue microarray revealed that breast tumors expressing human epidermal growth factor receptor 2 (HER2) showed higher expression levels of HMGA1 (P=0.007). In addition, higher HMGA1 expression levels were also observed in the ductal breast cancer cases compared with the lobular breast cancer cases (P=0.000). These findings establish the first link between HMGA1 and TGF-β1 in breast cancer, providing further evidence of the pivotal role of HMGA1 in breast cancer progression.
摘要：
Ur anium release into the environment is a threat to human health, and the mechanisms of cytotoxicity caused by uranium are not well-understood. To improve our understanding in this respect, we herein evaluated the effects of uranium exposure on normal rat hepatic BRL cells. As revealed by scanning electron microscopy and transmission electron microscope analysis, uranyl nitrate was found to be transformed into uranyl phosphate particles in the medium and taken up by BRL cells in an endocytotic uptake manner, which presumably initiates apoptosis of the cell, although soluble uranyl ion may also be toxic. The apoptosis of BRL cells upon uranium exposure was also confirmed by both the acridine orange and ethidium bromide double staining assay and the Annexin V/propidium iodide double staining assay. Further studies revealed that uranium induced the loss of mitochondrial membrane potential in a dose-dependent manner. Moreover, the uranium-induced apoptosis was found to be associated with the activation of caspase-3, caspase-8 and caspase-9, indicating both a mitochondria-dependent signaling pathway and a death receptor pathway by a crosstalk. This study provides new chemical and biological insights into the mechanism of uranium toxicity toward hepatic cells, which will help seek approaches for biological remediation of uranium.
作者机构：
[Xuyu Zu; Jing Zhong; Jingjing Tan; Li Tan; Dong Yang; Jianghua Liu; Renxian Cao; Gebo Wen] Institute of Clinical Medicine, the First Affiliated Hospital of University of South China
会议名称：
第八届中国肿瘤学术大会暨第十三届海峡两岸肿瘤学术会议
会议时间：
2014-09-11
会议地点：
济南
会议论文集名称：
第八届中国肿瘤学术大会暨第十三届海峡两岸肿瘤学术会议论文集
摘要：
<正>Background Both Transforming growth factor-beta1 signalling and HMGA1 have essential roles in the progression of breast cancer by inducing epithelial-mesenchymal transition,and the correlation betw
