共查询到20条相似文献,搜索用时 31 毫秒
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《Biochemical and biophysical research communications》2020,521(4):1003-1009
Helicobacter pylori (H. pylori) infection can promote the development of gastric cancer (GC); however, the underlying mechanism is not clear. FAM60A has been found showing high levels in some cancer cells, including lung cancer (A549), and pancreatic cancer (Capan-2) cell lines. Data in oncomine showed that FAM60A overexpression was an critical prognostic factor in GC. In this study, we showed that knockdown of FAM60A could revert the increase of proliferation and the decrease of apoptosis caused by H.pylori infection in HGC-27 and AGS cells. Conversely, FAM60A upregulation promoted proliferation and inhibited apoptosis in HGC-27 and AGS cells. We also found that the PI3K/AKT pathway inhibitor LY294002 could revert the changes caused by FAM60A upregulation in HGC-27 and AGS cells. Thus, our study provides evidence that FAM60A act as a carcinogen and suggests that H. pylori-induced upregulation of FAM60A may contribute to the development of gastric cancer. 相似文献
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Chemotherapy resistance is still a key hurdle in current hepatocellular carcinoma (HCC) treatment. Therefore, clarifying the molecular mechanisms contributing to this acquired resistance is urgent for the effective treatment of liver cancer. In this research, we observed that lncRNA FAM225A expression is dramatically up-regulated not only in HCC tissues and cell lines but also in sorafenib-resistant HepG2/SOR cells. Moreover, FAM225A knockdown significantly weakened HepG2/SOR cells resistance to sorafenib treatment by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Similar results were obtained from the tumor xenograft model in mice. Further mechanistic researches revealed that the direct interaction between FAM225A and miR-130a-5p, while miR-130a-5p negatively modulated Cyclin G1 (CCNG1) expression by targeting 3′UTR of CCNG1. MiR-130a-5p inhibition or CCNG1 overexpression could partially offset FAM225A knockdown-induced increased viability of HepG2/SOR cells in response to sorafenib challenge. Collectively, our findings provide evidence that FAM225A/miR-130a-5p/CCNG1 interaction network regulates the resistance of HCC cells to sorafenib treatment and could supply a possible strategy for restoring sorafenib sensitivity in HCC therapy. 相似文献
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《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2020,1867(2):118615
N-myc downstream-regulated gene 2 (NDRG2) as a tumor suppressor is frequently downregulated in human T-lymphotropic retrovirus (HTLV-1)-infected adult T-cell leukemia (ATL) and variety of cancers, and negatively regulates PI3K signaling pathways through dephosphorylation of PTEN with protein phosphatase 2A (PP2A). We recently identified that protein arginine methyltransferase 5 (PRMT5) is one of novel NDRG2 binding proteins and the knockdown of PRMT5 induces cell apoptosis with degradation of several signaling molecules. To investigate how the apoptosis is induced by the knockdown PRMT5 expression, heat shock protein 90 alpha (HSP90A) was identified as a binding protein for NDRG2 or PRMT5 by immunoprecipitation-mass analysis. NDRG2/PP2A complex inhibited arginine methyltransferase activity of PRMT5 through dephosphorylation at Serine 335 (S335); however, in NDRG2low ATL-related cells, highly phosphorylated PRMT5 at S335 was mainly localized in cytoplasm with binding to HSP90A, resulting in enhancing arginine-methylation at the middle domain (R345 and R386). Since knockdown of PRMT5 expression or forced expression of HSP90A with alanine replacement of R345 or R386 induced apoptosis with the degradation of client proteins in NDRG2low ATL-related and other cancer cells, we here identified that the novel arginine methylations of HSP90A are essential for maintenance of its function in NDRG2low ATL and other cancer cells. 相似文献
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Xinyu Liu Jun Zhang Lei Liu Yannan Jiang Jun Ji Ranlin Yan Zhenggang Zhu Yingyan Yu 《生物化学与生物物理学报:疾病的分子基础》2018,1864(9):2835-2844
IRX1 is originally characterized as a tumor suppressor gene of gastric cancer (GC) by our group based on serially original studies. However, the molecular regulatory mechanisms of IRX1 are not clear yet. Here, we identified protein arginine methyltransferase 5 (PRMT5) as a major upstream regulator of IRX1 for determining GC progression. Expression of PRMT5 was significantly increased in human GC tissues (433 out of 602 cases, 71.93%) compared with normal gastric mucosa, and exhibited diagnostic and prognostic potential. Overexpression of PRMT5 promoted tumorigenicity and metastasis of GC cells, while knockdown of PRMT5 abrogated tumorigenicity and metastasis of GC cells in vitro and in vivo. By co-immunoprecipitation and chromatin immunoprecipitation assays, we proved that PRMT5 elevated methylation levels of tumor suppressor IRX1 promoter via recruiting DNMT3A at promoter region. Knockdown of PRMT5 in SGC7901 and NCI-N87 cells decreased the recruitment of DNMT3A at IRX1 promoter, and reduced the methylation level of IRX1 promoter, then re-activated IRX1 expression. Whereas, overexpression of PRMT5 could epigenetically suppress IRX1 expression. Overall, PRMT5 promoted tumorigenicity and metastasis of gastric cancer cells via epigenetic silencing of IRX1. Targeting PRMT5 in GC might inhibit the malignant characters of GC and drawing a novel therapeutic potential. 相似文献
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Kais Kasem Vinod Gopalan Ali Salajegheh Cu-Tai Lu Robert A. Smith Alfred K.-Y. Lam 《Experimental cell research》2014
The aims of the present study are to investigate the clinicopathological correlations of JK-1(FAM134B) expression and its relationship to carcinogenesis in a colorectal adenoma–adenocarcinoma model. JK-1(FAM134B) protein expression was studied in a colon cancer cell line by Western blot and immunocytochemistry. JK-1(FAM134B) expression profiles at mRNA and protein levels were investigated in cancer tissues from 236 patients with colorectal adenocarcinoma and 32 patients with colorectal adenoma using real-time polymerase chain reaction and immunohistochemistry. The findings were then correlated with the clinicopathological features of these tumours. JK-1(FAM134B) protein was demonstrated in the colon cancer cells by Western blot. The protein was located in the nuclei of the tumour cells at both cellular and tissue levels. In colorectal adenocarcinomas, lower levels of JK-1(FAM134B) protein expression were associated with younger age (p=0.032), larger tumour size (p=0.004), advanced cancer stages (p=0.016) and higher rates of cancer recurrence (p=0.04). Also, lower levels of JK-1(FAM134B) mRNA expression were associated with advanced cancer stages (p=0.02) and presence of lymphovascular invasion (p=0.014). Higher JK-1(FAM134B) mRNA and protein expression levels were identified in adenomas and non-neoplastic mucosae, compared to carcinomas (p=0.005). To conclude, JK-1(FAM134B) mRNA expression and JK1 (FAM134B) protein levels varied with the different stages of progression of colorectal tumours. The expression levels of the gene were associated with clinicopathological features in patients with colorectal adenocarcinoma suggesting that JK-1(FAM134B) gene has roles in controlling some steps in the development of the invasive phenotypes from colorectal adenoma to early staged as well as advanced staged colorectal adenocarcinomas. 相似文献
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Youli Zhang Dawei Wang Meiting Zhang Hong Wei Ying Lu Yaocheng Sun Meng Zhou Shuming Gu Wen Feng Huizhi Wang Jian Zeng Aihua Gong Min Xu 《Experimental cell research》2018,362(1):43-50
Protein arginine methyltransferase 1 (PRMT1) is up-regulated and promotes migration, invasion and proliferation in wide range of cancers. However, we for the first time identify that PRMT1 promotes migration and invasion and inhibits proliferation in gastric cancer cells, a phenomenon called “migration-proliferation dichotomy”. First, we find that PRMT1 overexpression promotes migration and invasion and inhibits proliferation, whereas PRMT1 knockdown reverses the above abilities. Next, PRMT1 reduces the expression of epithelial marker E-cadherin and increases the expression of mesenchymal markers including N-cadherin, Vimentin, snail and β-catenin in gastric cancer cells. Furthermore, our studies show that PRMT1 silencing promotes the phosphorylation of LATS1, and then induces YAP phosphorylation, while overexpression of PRMT1 down-regulates the phosphorylation of LATS1 and YAP, indicating that PRMT1 inhibits EMT probably via Hippo signaling. Collectively, the present study reveals important roles of PRMT1 in progression of gastric cancer. Given the dual functions of PRMT1, it is as a potential drug target of gastric cancer with extreme caution. 相似文献
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FAM3家族是2002年新发现的一个细胞因子样基因家族,由FAM3A、FAM3B、FAM3C和FAM3D4个成员组成,分别编码含有224—235个氨基酸残基的多肽,它们在二级结构上都具有4个α螺旋。这种二级结构特征与一些细胞因子相似。本文综述了FAM3家族成员的基因定位及结构、基因表达和分泌的调控,以及生理功能和病理意义的研究进展。 相似文献
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96序列相似的家庭成员A和B(family with sequence similarity 96 member A and B,FAM96A和FAM96B)是属于MIP18(MMS19-interacting protein of 18 kD)家族的2个高度保守的同源蛋白,MIP18是与有丝分裂纺锤体相关的MMDX(MMS19-MIP18-XPD)复合体的亚基。研究表明,FAM96A和FAM96B在人胃肠道间质瘤、结肠癌、肝癌、胃癌和乳腺癌等多种肿瘤组织中的表达显著降低,提示其可能是作为潜在的抑癌基因参与肿瘤的发生发展,但目前关于FAM96A和FAM96B在肿瘤发生发展过程中的作用机理并不十分清楚。此外,研究发现FAM96A和FAM96B可通过与其他不同的蛋白质相互作用在体内发挥多种不同的功能。因此,就目前对于FAM96A和FAM96B结构和功能的研究所取得的进展进行了回顾与总结,并对其在肿瘤发生发展中的分子机制和相互作用蛋白鉴定的研究前景进行了展望,以期为临床上将FAM96A和FAM96B作为新的肿瘤诊断标志物和治疗靶点奠定基础,并为揭示二者在体内更多的新功能提供依据。 相似文献
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A recent proteomics study identified FAM129B or MINERVA as a target of the MAP kinase (Erk1/2) signaling cascade in human melanoma cells. Phosphorylation of the protein was found to promote cell invasion and the dissociation of the protein from the cell-cell junctions. Suppression of apoptosis during metastasis is a prerequisite for the survival and spread of cancer cells. During apoptosis, the adherens junctions are disassembled as the dying cell retracts, and new contacts are formed between normal neighboring cells. In this study, we show that FAM129B was cytosolic in exponentially growing HeLa cells but was translocated to the adherens junctions where it colocalized with β-catenin whenever contact between two or more cells was established. Silencing the FAM129B gene expression by specific siRNAs did not induce apoptosis or inhibit the growth of HeLa cells. However, when apoptosis was induced by exposure to TNFα/cycloheximide or other apoptotic signaling molecules, the onset of apoptosis was accelerated 3-4-fold when FAM129B was depleted. Annexin V binding, the inactivation of the DNA repair enzyme, poly(ADP-ribose) polymerase, and the activation of the caspases occurred more rapidly in the cells lacking FAM129B. The rapid induction of apoptosis in FAM129B knockdown cells was reversed by co-transfection with recombinant FAM129B, indicating that its effect on apoptosis was specific. As apoptosis proceeded, FAM129B was degraded and disappeared from the plasma membrane. Thus, one crucial facet of the mechanism by which FAM129B promotes cancer cell invasion is likely to be the suppression of apoptosis. 相似文献
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Hui Shan Yunbo Yang Xuhui Zhu Xiuwu Han Peng Zhang Xiaodong Zhang 《Journal of cellular biochemistry》2019,120(3):4687-4693
FAM83H-AS1, also known as oncogenic long noncoding RNA (lncRNA)-3, is a novel lncRNA that has been suggested to be dysregulated in a variety of human cancers. However, the expression status and function of FAM83H-AS1 in bladder cancer are still unknown. The object of our study is to explore the clinical value of FAM83H-AS1 in patients with bladder cancer and the biological function of FAM83H-AS1 in bladder cancer cells. In our results, the expression of FAM83H-AS1 was obviously elevated in bladder cancer tissue samples and bladder cancer cell lines compared with adjacent normal tissue samples and normal bladder epithelial cell lines, respectively. In addition, high expression of FAM83H-AS1 was associated with advanced clinical stage and the presence of muscularis invasion and served as an independent poor prognostic factor for overall survival in patients with bladder cancer. The loss-of-function study showed that silencing FAM83H-AS1 expression suppressed cell proliferation, migration, and invasion and induced cycle arrest at G0/G1 phase. In conclusion, FAM83H-AS1 is involved in the progression of bladder cancer and serves as a prognostic biomarker and potential therapeutic target for patients with bladder cancer. 相似文献
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Zhencong Chen Zhengyang Hu Qihai Sui Yiwei Huang Mengnan Zhao Ming Li Jiaqi Liang Tao Lu Cheng Zhan Zongwu Lin Fenghao Sun Qun Wang Lijie Tan 《International journal of biological sciences》2022,18(2):522
Background: Lung adenocarcinoma (LUAD), the major subtype of lung cancer, is among the leading cause of cancer-related death worldwide. Energy-related metabolic reprogramming metabolism is a hallmark of cancer shared by numerous cancer types, including LUAD. Nevertheless, the functional pathways and molecular mechanism by which FAM83A-AS1 acts in metabolic reprogramming in lung adenocarcinoma have not been fully elucidated.Methods: We used transwell, wound-healing scratch assay, and metabolic assays to explore the effect of FAM83A-AS1 in LUAD cell lines. Western blotting, Co-IP assays, and ubiquitination assays were used to detect the effects of FAM83A-AS1 on HIF-1α expression, degradation, and its binding to VHL. Moreover, an in vivo subcutaneous tumor formation assay was used to detect the effect of FAM83A-AS1 on LUAD.Results: Herein, we identified FAM83A-AS1 as a metabolism-related lncRNA, which was highly correlated with glycolysis, hypoxia, and OXPHOS pathways in LUAD patients using bioinformatics analysis. In addition, we uncovered that FAM83A-AS1 could promote the migration and invasion of LUAD cells, as well as influence the stemness of LUAD cells in vivo and vitro. Moreover, FAM83A-AS1 was shown to promote glycolysis in LUAD cell lines in vitro and in vivo, and was found to influence the expression of genes related to glucose metabolism. Besides, we revealed that FAM83A-AS1 could affect glycolysis by regulating HIF-1α degradation. Finally, we found that FAM83A-AS1 knockdown could inhibit tumor growth and suppress the expression of HIF-1α and glycolysis-related genes in vivo.Conclusion: Our study demonstrates that FAM83A-AS1 contributes to LUAD proliferation and stemness via the HIF-1α/glycolysis axis, making it a potential biomarker and therapeutic target in LUAD patients. 相似文献