scholarly journals A Four-Methylated lncRNAs-Based Prognostic Signature for Hepatocellular Carcinoma

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 908
Author(s):  
Le-En Liao ◽  
Dan-Dan Hu ◽  
Yun Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prediction Model ◽  
Cell Lines ◽  
Prediction Models ◽  
Hepatoma Cell ◽  
Critical Role ◽  
The Cancer Genome Atlas ◽  
Roc Curve Analysis ◽  
Data Set ◽  
Hepatoma Cell Lines

Currently, an increasing number of studies suggest that long non-coding RNAs (lncRNAs) and methylation-regulated lncRNAs play a critical role in the pathogenesis of various cancers including hepatocellular carcinoma (HCC). Therefore, methylated differentially expressed lncRNAs (MDELs) may be critical biomarkers of HCC. In this study, 63 MDELs were identified by screening The Cancer Genome Atlas (TCGA) HCC lncRNAs expression data set and lncRNAs methylation data set. Based on univariate and multivariate survival analysis, four MDELs (AC025016.1, LINC01164, LINC01183 and LINC01269) were selected to construct the survival prognosis prediction model. Through the PI formula, the study indicates that our new prediction model performed well and is superior to the traditional staging method. At the same time, compared with the previous prediction models reported in the literature, the results of time-dependent receiver operating characteristic (ROC) curve analysis show that our 4-MDELs model predicted overall survival (OS) stability and provided better prognosis. In addition, we also applied the prognostic model to Cancer Cell Line Encyclopedia (CCLE) cell lines and classified different hepatoma cell lines through the model to evaluate the sensitivity of different hepatoma cell lines to different drugs. In conclusion, we have established a new risk scoring system to predict the prognosis, which may have a very important guiding significance for the individualized treatment of HCC patients.

scholarly journals Multiplexed Proteomic Approach for Identification of Serum Biomarkers in Hepatocellular Carcinoma Patients with Normal AFP

2020 ◽  
Vol 9 (2) ◽  
pp. 323
Author(s):  
Young-Sun Lee ◽  
Eunjung Ko ◽  
Eileen L. Yoon ◽  
Young Kul Jung ◽  
Ji Hoon Kim ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Cell Lines ◽  
Cellular Proliferation ◽  
Hepatoma Cell ◽  
Multiple Reaction Monitoring ◽  
Serum Levels ◽  
Human Hepatoma Cell ◽  
Hepatoma Cell Lines ◽  
Proteomic Approach

Alpha fetoprotein (AFP) has been used as a serologic indicator of hepatocellular carcinoma (HCC). We aimed to identify an HCC-specific serum biomarker for diagnosis using a multiplexed proteomic technique in HCC patients with normal AFP levels. A total of 152 patients were included from Guro Hospital, Korea University. Among 267 identified proteins, 28 and 86 proteins showed at least a two-fold elevation or reduction in expression, respectively. Multiple reaction monitoring (MRM) analysis of 41 proteins revealed 10 proteins were differentially expressed in patients with liver cirrhosis and HCC patients with normal AFP. A combination of tripartite motif22 (Trim22), seprase, and bone morphogenetic protein1 had an area under receiver operating characteristic of 0.957 for HCC diagnosis. Real-time PCR and western blot analysis of the paired tumor/non-tumor liver tissue in HCC revealed a reduced expression of Trim22 in the tumor tissue. Also, serum levels of Trim22 were significantly reduced in HCC patients with normal AFP compared to those with liver cirrhosis (p = 0.032). Inhibition of Trim22 increased cellular proliferation in human hepatoma cell lines, whereas overexpression of Trim22 decreased cellular proliferation in hepatoma cell lines. In conclusion, the combination of three serum markers improved the chance of diagnosing HCC. MRM-based quantification of the serum protein in patients with normal AFP provides the potential for early diagnosis of HCC.

Artocarpus communis Induces Autophagic Instead of Apoptotic Cell Death in Human Hepatocellular Carcinoma Cells

2015 ◽  
Vol 43 (03) ◽  
pp. 559-579 ◽  
Author(s):  
Cheng-Wei Tzeng ◽  
Wen-Sheng Tzeng ◽  
Liang-Tzung Lin ◽  
Chiang-Wen Lee ◽  
Ming-Hong Yen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Death ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Hepatoma Cell ◽  
Apoptotic Cell Death ◽  
Human Hepatocellular Carcinoma ◽  
Acridine Orange Staining ◽  
Hepatoma Cell Lines

For centuries, natural plant extracts have played an important role in traditional medicine for curing and preventing diseases. Studies have revealed that Artocarpus communis possess various bioactivities, such as anti-inflammation, anti-oxidant, and anticancer activities. A. communis offers economic value as a source of edible fruit, yields timber, and is widely used in folk medicines. However, little is known about its molecular mechanisms of anticancer activity. Here, we demonstrate the antiproliferative activity of A. communis methanol extract (AM) and its dichloromethane fraction (AD) in two human hepatocellular carcinoma (HCC) cell lines, HepG2 and PLC/PRF/5. Colony assay showed the long-term inhibitory effect of both extracts on cell growth. DNA laddering and immunoblotting analyses revealed that both extracts did not induce apoptosis in the hepatoma cell lines. AM and AD-treated cells demonstrated different cell cycle distribution compared to UV-treated cells, which presented apoptotic cell death with high sub-G1 ratio. Instead, acridine orange staining revealed that AM and AD triggered autophagosome accumulation. Immunoblotting showed a significant expression of autophagy-related proteins, which indicated the autophagic cell death (ACD) of hepatoma cell lines. This study therefore demonstrates that A. communis AM and its dichloromethane fraction can induce ACD in HCC cells and elucidates the potential of A. communis extracts for development as anti tumor therapeutic agents that utilize autophagy as mechanism in mediating cancer cell death.

scholarly journals GSTZ1 sensitizes hepatocellular carcinoma cells to sorafenib-induced ferroptosis via inhibition of NRF2/GPX4 axis

2020 ◽  
Author(s):  
Qiujie Wang ◽  
Bin Cheng ◽  
Qiang Xue ◽  
Qingzhu Gao ◽  
Ailong Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Hepatoma Cell ◽  
Redox Homeostasis ◽  
Lipid Peroxides ◽  
Tumor Growth Inhibition ◽  
Related Factor ◽  
Hepatoma Cell Lines

AbstractIncreasing evidence supports that ferroptosis plays an important role in tumor growth inhibition. Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, has been shown to induce ferroptosis in hepatocellular carcinoma (HCC). However, some hepatoma cell lines are less sensitive to sorafenib-induced ferroptotic cell death. Glutathione S-transferase zeta 1 (GSTZ1), an enzyme in the catabolism of phenylalanine, has been found to negatively regulate the master regulator of cellular redox homeostasis nuclear factor erythroid 2-related factor 2 (NRF2). This study aimed to investigate the role of GSTZ1 in sorafenib-induced ferroptosis in HCC cell lines and determine the involved molecular mechanisms. Mechanistically, GSTZ1 depletion enhanced the activation of the NRF2 pathway and increased the glutathione peroxidase 4 (GPX4) level, thereby suppressing sorafenib-induced ferroptosis. The combination of sorafenib and RSL3, a GPX4 inhibitor, significantly inhibited GSTZ1 deficient cell viability and promoted ferroptosis, accompanied with ectopic increases of iron and lipid peroxides. An in vivo experiment showed that the combination of sorafenib and RSL3 had a synergic therapeutic effect on HCC progression in Gstz1−/− mice. In conclusion, GSTZ1 was significantly downregulated in sorafenib resistant hepatoma cells. GSTZ1 enhanced sorafenib-induced ferroptosis by inhibiting the NRF2/GPX4 axis in HCC cells. GSTZ1 deficiency was resistant to sorafenib-induced ferroptosis and is, therefore, a potential therapeutic approach for treating HCC by synergizing sorafenib and RSL3 to induce ferroptosis.

scholarly journals Identification of PAFAH1B3 as Candidate Prognosis Marker and Potential Therapeutic Target for Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Weikang Xu ◽  
Xinyu Lu ◽  
Jing Liu ◽  
Qianhui Chen ◽  
Xuan Huang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Lines ◽  
Critical Role ◽  
Disease Free Survival ◽  
The Cancer Genome Atlas ◽  
Transwell Assay ◽  
Mutational Status ◽  
Prognosis Marker ◽  
Hcc Cells

BackgroundHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. PAFAH1B3 plays an important role on occurrence and development in a variety tumor. However, the function of PAFAH1B3 in HCC remains unclear.MethodsThe TIMER, ONCOMINE, Human Protein Atlas (HPA), GEPIA, The Cancer Genome Atlas (TCGA), HCCDB, UALCAN and LinkedOmics database were used to analyze the prognostic value, co-expression genes and regulator networks of PAFAH1B3 in HCC. siRNA transfections and inhibitor of PAFAH1B3 P11 were used to verify the anti-tumor effect on HCC cell lines. Gene expression was detected by qRT-PCR. The functions of PAFAH1B3 downregulation in HCC cell lines were investigated using cell cycle analysis, apoptosis detection, CCK8 assay and transwell assay. Western blot was used to evaluate the role of PAFAH1B3 on metabolic pathways in HCC cells.ResultsBased on the data from databases, the expression of PAFAH1B3 was remarkably increased in HCC patients. High expression of PAFAH1B3 was associated with poorer overall survival (OS) and disease-free survival (DFS). And PAFAH1B3 was notably linked to age, sex, grade, stage, race, and TP53 mutational status. Then, the functional network analysis showed PAFAH1B3 may be involved in HCC through cell cycle, cell metabolism, spliceosome, and RNA transport. Furthermore, the mRNA expression of PAFAH1B3 was also increased in HCC cell lines. Flow cytometry analysis showed that PAFAH1B3 manipulated apoptosis and cell cycle regulation. CCK8 assay showed that PAFAH1B3 silencing or pharmacologic inhibitor of PAFAH1B3 inhibited the proliferation of HepG2, Huh7 and MHCC-97H cells. Transwell assay results showed that PAFAH1B3 silencing also significantly impaired the invasion and migratory ability of HCC cells. In addition, PAFAH1B3 silencing significantly downregulated the expression of glycolysis and lipid synthesis signaling pathways.ConclusionOur findings suggested that PAFAH1B3 plays a critical role in progression of HCC. PAFAH1B3 as a prognosis marker and potential target for HCC has prospective clinical significance.

Glycomic Analysis of Alpha-Fetoprotein L3 in Hepatoma Cell Lines and Hepatocellular Carcinoma Patients

2008 ◽  
Vol 7 (6) ◽  
pp. 2222-2233 ◽  
Author(s):  
Takatoshi Nakagawa ◽  
Eiji Miyoshi ◽  
Takayuki Yakushijin ◽  
Naoki Hiramatsu ◽  
Takumi Igura ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Alpha Fetoprotein ◽  
Hepatoma Cell Lines

scholarly journals Melatonin Inhibits the Progression of Hepatocellular Carcinoma through MicroRNA Let7i-3p Mediated RAF1 Reduction

2018 ◽  
Vol 19 (9) ◽  
pp. 2687 ◽  
Author(s):  
Tong-Hong Wang ◽  
Chuen Hsueh ◽  
Chin-Chuan Chen ◽  
Wan-Syuan Li ◽  
Chau-Ting Yeh ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Lines ◽  
Hepatoma Cell ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Small Rna Sequencing ◽  
Human Hepatoma Cell ◽  
Melatonin Treatment ◽  
Hepatoma Cell Lines ◽  
Mitogen Activated Protein

Melatonin is the main pineal hormone that relays light/dark-cycle information to the circadian system. Recent studies have examined the intrinsic antitumor activity of melatonin in various cancers, including hepatocellular carcinoma (HCC), the primary life-threatening malignancy in both sexes in Taiwan. However, the detailed regulatory mechanisms underlying melatonin’s anti-HCC activity remain incompletely understood. Here, we investigated the mechanisms by which the anti-HCC activity of melatonin is regulated. Human hepatoma cell lines were treated with 1 and 2 mM melatonin, and functional assays were used to dissect melatonin’s antitumor effect in HCC; small-RNA sequencing was performed to identify the microRNAs (miRNAs) involved in the anti-HCC activity of melatonin; and quantitative RT-PCR and Western blotting were used to elucidate how miRNAs regulate melatonin-mediated HCC suppression. Melatonin treatment at both doses strongly inhibited the proliferation, migration and invasion capacities of Huh7 and HepG2 cell lines, and melatonin treatment markedly induced the expression of the miRNA let7i-3p in cells. Notably, transfection of cells with a let7i-3p mimic drastically reduced RAF1 expression and activation of mitogen-activated protein kinase signaling downstream from RAF1, and rescue-assay results demonstrated that melatonin inhibited HCC progression by modulating let7i-3p-mediated RAF1 suppression. Our findings support the view that melatonin treatment holds considerable promise as a therapy for HCC.

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