scholarly journals Promoter Methylation ofSFRP3Is Frequent in Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Ya-Wen Lin ◽  
Yu-Lueng Shih ◽  
Gi-Shih Lien ◽  
Fat-Moon Suk ◽  
Chung-Bao Hsieh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Mrna Expression ◽  
Cell Lines ◽  
Promoter Methylation ◽  
Promoter Hypermethylation ◽  
Polymerase Chain ◽  
Related Proteins ◽  
And Control

Oncogenic activation of the Wnt/β-catenin signaling pathway is common in human cancers. The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications in carcinogenesis. Because there have been no reports about the role ofSFRP3in hepatocellular carcinoma (HCC), we investigated the level of methylation and transcription ofSFRP3. Four HCC cell lines, 60 HCCs, 23 cirrhosis livers, 37 chronic hepatitis livers, and 30 control livers were prescreened forSFRP3promoter methylation by methylation-specific polymerase chain reaction (MS-PCR) and bisulfite sequencing.SFRP3promoter methylation was observed in 100%, 60%, 39.1%, 16.2%, and 0% in HCC cell lines, primary HCCs, cirrhosis livers, chronic hepatitis livers, and control livers, respectively. Demethylation treatment with 5-aza-2′-deoxycytidine in HCC cells restored or increased theSFRP3mRNA expression. We next used quantitative MS-PCR (QMSP) to analyze the methylation level ofSFRP3in 60 HCCs and their corresponding nontumor tissues. Methylation ofSFRP3promoter region in HCCs increased significantly compared with control tissues. There is a positive correlation between promoter hypermethylation andSFRP3mRNA downregulation. Our data suggest that promoter hypermethylation ofSFRP3is a common event in HCCs and plays an important role in regulation ofSFRP3mRNA expression.

scholarly journals Role of tight junction-associated MARVEL protein marvelD3 in migration and Epithelial–Mesenchymal Transition of hepatocellular carcinoma

2021 ◽  
Author(s):  
Yanmeng Li ◽  
Teng Li ◽  
Donghu Zhou ◽  
Jia Wei ◽  
Zhenkun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tight Junction ◽  
Tumor Cell ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Mesenchymal Transition ◽  
And Migration ◽  
Related Proteins ◽  
Hcc Cells

Abstract BackgroundTight junction (TJ) imbalance is associated with hepatocellular carcinoma (HCC). MarvelD3, which contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain similarly to occludin and tricellulin, is a recently identified integral membrane protein that forms TJs. However, little is known about the possible roles of marvelD3 in epithelial–mesenchymal transition (EMT) and metastasis of HCC. We aimed to demonstrate the role of marvelD3 in inhibiting HCC EMT and migration and further explore the underlying molecular mechanisms.MethodsMarvlD3 expression was assessed in HCC and normal liver tissues. Changes in marvelD3 expression were analyzed during transforming growth factor β1 (TGF-β1) and snail/slug-induced EMT. MarvelD3 knockdown HCC cell lines were established using marvelD3-siRNA to analyze correlations between marvelD3 and EMT-related proteins. Tumor cell behaviors were analyzed in marvelD3 knockdown HCC cells. Associations between marvelD3 and genes in the nuclear factor (NF)-κB pathway were also analyzed.ResultsLoss of marvelD3 expression was significantly correlated with the occurrence and TNM stage of HCC. MarvelD3 was downregulated in HCC cells with TGF-β and snail/slug-induced EMT. Expression of marvelD3 protein was significantly associated with E-cadherin and vimentin in HCC cell lines. Knockdown of marvelD3 promoted tumor cell migration concomitant with activation of the NF-κB signaling pathway and increased matrix metallopeptidase 9 expression.ConclusionsOur study demonstrated that MarvelD3 inhibited EMT and migration of HCC cells via NF-κB signaling pathway. This suggests that marvelD3 is a novel potential biomarker for the treatment and prognosis of HCC.

Epigenetic Inactivation of the Secreted Frizzled-Related Protein Gene Family in Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2131-2131
Author(s):  
Edgar Jost ◽  
Deniz Gezer ◽  
Stefan Wilop ◽  
James G. Herman ◽  
Rainhardt Osieka ◽  
...  
Keyword(s):  
Cell Lines ◽  
Wnt Pathway ◽  
Methylation Status ◽  
Cpg Islands ◽  
Promoter Hypermethylation ◽  
Aberrant Methylation ◽  
Chain Reaction ◽  
Genetic Aberrations ◽  
Polymerase Chain

Abstract Multiple myeloma (MM) is a B-cell neoplasm that is characterized by the accumulation of malignant plasma cells in the bone marrow. Previous molecular studies have largely focused on acquired genetic aberrations in MM. There is increasing evidence that in addition to genetic aberrations epigenetic processes play a major role in carcinogenesis. Aberrant methylation of CpG islands near gene promoter regions is the most widely studied epigenetic abnormality in human malignancies and is associated with loss of gene function. This epigenetic event acts as an alternative to mutations and deletions to disrupt tumor suppressor gene function. The Wnt pathway has been recognized to be essential for normal organ development, and a role for Wnt signal transduction at several stages of lymphocyte differentiation and in the self-renewal of hematopoietic stem cells could be demonstrated. Alterations in the Wnt pathway have been shown to contribute to the pathogenesis of various human malignancies. Epigenetic silencing of the family of secreted frizzled-related proteins (SFRPs), which act as Wnt antagonists, was recently reported in several solid tumors and in acute lymphoblastic leukemia. In order to investigate the potential role of abnormal Wnt signaling in MM, we determined the methylation status of the promoter-associated CpG islands of SFRP-1, 2, 4 and 5 in the MM cell lines U266, LP-1, RPMI-8226 and OPM-2. Methylation-specific polymerase chain reaction (MSP) analysis revealed that promoter hypermethylation of the SFRP genes was a frequent event in MM cell lines (SFRP-1: 2/4, SFRP-2: 2/4, SFRP-4: 1/4 and SFRP-5: 3/4). Aberrant methylation of SFRP-1 and SFRP-2 in MM cell lines was associated with transcriptional silencing, as determined by real-time reverse transcriptase polymerase chain reaction. Treatment of cell lines that carry a hypermethylated SFRP-1 and SFRP-2 gene, respectively, with the demethylating agent 5-aza-2′-deoxycytidine resulted in gene reexpression. We then analyzed by MSP the methylation status of SFRP-1, 2, 4 and 5 in 76 specimens obtained from MM patients. The frequency of aberrant methylation among the primary patient samples was 38.2% (29/76) for SFRP-1, 59.2% (45/76) for SFRP-2, 2.6% (2/76) for SFRP-4 and 7.6% (6/76) for SFRP-5. There was a high incidence of concomitant hypermethylation of SFRP-1 and SRFP-2. We conclude that promoter hypermethylation of the SFRP genes is a novel epigenetic event in MM that may contribute to aberrant activation of the Wnt pathway. Further studies are warranted to elucidate the functional consequences of aberrant Wnt signaling by downregulation of the SFRP genes in the pathogenesis of MM. Additionally, the increasing evidence for the important role of DNA methylation changes in malignant plasma cell disorders may serve as a basis for the use of epigenetically targeted therapeutic approaches in MM in the future.

scholarly journals Iron-sulphur cluster biogenesis factor LYRM4 is a novel prognostic biomarker associated with immune infiltrates in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yilin Pang ◽  
Guoqiang Tan ◽  
Xunjun Yang ◽  
Yuanshan Lin ◽  
Yao Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Cell Lines ◽  
Immune Cell ◽  
Prognostic Biomarker ◽  
Metabolic Reprogramming ◽  
Future Research ◽  
Aconitate Hydratase ◽  
Tumour Thrombus

Abstract Background LYRM4 is necessary to maintain the stability and activity of the human cysteine desulfurase complex NFS1-LYRM4-ACP. The existing experimental results indicate that cancer cells rely on the high expression of NFS1. However, the role of LYRM4 in liver hepatocellular carcinoma (LIHC) remains unclear. Methods In this study, we combined bioinformatics analysis and clinical specimens to evaluate the mRNA, protein expression, and gene regulatory network of LYRM4 in LIHC. Furthermore, we detected the activity of several classical iron-sulphur proteins in LIHC cell lines through UV-vis spectrophotometry. Results The mRNA and protein levels of LYRM4 were upregulated in LIHC. Subsequent analysis revealed that the LYRM4 mRNA expression was related to various clinical stratifications, prognosis, and survival of LIHC patients. In addition, the mRNA expression of LYRM4 was significantly associated with ALT, tumour thrombus, and encapsulation of HBV-related LIHC patients. IHC results confirmed that LYRM4 was highly expressed in LIHC tissues and showed that the expression of LYRM4 protein in LIHC was significantly correlated with age and serum low-density lipoprotein (LDL) and triglyceride (TG) content. In particular, the mRNA expression of key iron- sulphur proteins POLD1 and PRIM2 was significantly overexpressed and correlated with poor prognosis in LIHC patients. Compared with hepatocytes, the activities of mitochondrial complex I and aconitate hydratase (ACO2) in LIHC cell lines were significantly increased. These results indicated that the iron-sulphur cluster (ISC) biosynthesis was significantly elevated in LIHC, leading to ISC-dependent metabolic reprogramming. Changes in the activity of ISC-dependent proteins may also occur in paracancerous tissues. Further analysis of the biological interaction and gene regulation networks of LYRM4 suggested that these genes were mainly involved in the citric acid cycle and oxidative phosphorylation. Finally, LYRM4 expression in LIHC was significantly positively correlated with the infiltrating levels of six immune cell types, and both factors were strongly associated with prognosis. Conclusion LYRM4 could be a novel prognostic biomarker and molecular target for LIHC therapy. In particular, the potential regulatory networks of LYRM4 overexpression in LIHC provide a scientific basis for future research on the role of the ISC assembly mechanism and LYRM4-mediated sulphur transfer routes in carcinogenesis.

Steroid Formation in Osteoblast-Like Cells

1998 ◽  
Vol 26 (1) ◽  
pp. 1-12 ◽  
Author(s):  
H Saito ◽  
T Yanaihara
Keyword(s):  
Cell Lines ◽  
Messenger Ribonucleic Acid ◽  
Steroid Sulphatase ◽  
Menopausal Women ◽  
Hormonal Action ◽  
Polymerase Chain ◽  
Post Menopausal ◽  
Receptor Mrnas

For preventing the reduction of bone mass in post-menopausal women, oestrogen replacement is known to be useful and the importance of sex steroids in bone metabolism in both sexes is well established. The presence of steroid-converting-enzyme activities in various osteoblast and osteoblast-like cells has been demonstrated using in vitro culture systems. In the present study, we assessed the expression of messenger ribonucleic acid (mRNA) for aromatase, steroid sulphatase, 5α-reductase, 17β-hydroxysteroid dehydrogenase (17β-HSD) and 3β-HSD by reverse transcription-polymerase chain reaction in the human osteoblast-like cell lines, MG 63 and HOS. Oestrogen, androgen and progesterone receptor mRNAs were also measured. Expression of mRNA for these enzymes and receptors was found in both cell lines without induction. From these and previous findings, we conclude that osteoblast-like cells have the capacity to form biologically potent oestrogens and androgens from peripheral circulating steroids. This may indicate an important role of bone in facilitating hormonal action.

Quantitative proteomics identifies FOLR1 to drive sorafenib resistance via activating autophagy in hepatocellular carcinoma cells

2021 ◽  
Author(s):  
Hongwei Chu ◽  
Changqing Wu ◽  
Qun Zhao ◽  
Rui Sun ◽  
Kuo Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Folate Receptor ◽  
Mass Spectrometry Analysis ◽  
Label Free ◽  
Spectrometry Analysis ◽  
Underlying Mechanisms ◽  
Related Proteins ◽  
Hcc Cells

Abstract Sorafenib is commonly used to treat advanced human hepatocellular carcinoma (HCC). However, clinical efficacy has been limited by drug resistance. In this study, we used label-free quantitative proteomic analysis to systematically investigate the underlying mechanisms of sorafenib resistance in HCC cells. A total of 1709 proteins were confidently quantified. Among them, 89 were differentially expressed, and highly enriched in the processes of cell-cell adhesion, negative regulation of apoptosis, response to drug and metabolic processes involving in sorafenib resistance. Notably, folate receptor α (FOLR1) was found to be significantly upregulated in resistant HCC cells. In addition, in-vitro studies showed that overexpression of FOLR1 decreased the sensitivity of HCC cells to sorafenib, whereas siRNA-directed knockdown of FOLR1 increased the sensitivity of HCC cells to sorafenib. Immunoprecipitation-mass spectrometry analysis suggested a strong link between FOLR1 and autophagy related proteins. Further biological experiments found that FOLR1-related sorafenib resistance was accompanied by the activation of autophagy, whereas inhibition of autophagy significantly reduced FOLR1-induced cell resistance. These results suggest the driving role of FOLR1 in HCC resistance to sorafenib, which may be exerted through FOLR1-induced autophagy. Therefore, this study may provide new insights into understanding the mechanism of sorafenib resistance.

scholarly journals Promoter methylation and mRNA expression of DKK-3 and WIF-1 in hepatocellular carcinoma

2009 ◽  
Vol 15 (21) ◽  
pp. 2595 ◽  
Author(s):  
Zhen Ding ◽  
Ye-Ben Qian ◽  
Li-Xin Zhu ◽  
Qi-Ru Xiong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Promoter Methylation

Evaluating the role of transient elastography post chronic hepatitis C treatment to predict hepatocellular carcinoma

2020 ◽  
Vol 73 (5) ◽  
pp. 1287-1289
Author(s):  
Jacob H. Charette ◽  
Kelly W. Burak ◽  
Carla S. Coffin ◽  
Stephen E. Congly ◽  
Samuel S. Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis C ◽  
Chronic Hepatitis C ◽  
Transient Elastography ◽  
Hepatitis C Treatment
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