scholarly journals mRNA Transcriptomic Profiling of Human Hepatocellular Carcinoma Cells HepG2 Treated with Catharanthus roseus-Silver Nanoparticles

2021 ◽  
Author(s):  
Nur Asna Azhar ◽  
Siti Aishah Abu Bakar ◽  
Marimuthu Citartan ◽  
Nor Hazwani Ahmad
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Transcriptomic Profiling ◽  
Cycle Arrest ◽  
Cancer Nanomedicine ◽  
Normal Human Liver ◽  
Ic50 Values ◽  
Normal Human ◽  
Biosynthesized Agnps ◽  
Aberrant Gene

Background: The demand in the development of cancer nanomedicine has increased due to various limitations in conventional cancer therapy. This study assessed the mRNA transcriptomic profiling of human HepG2 cells exposed to C. roseus-AgNPs. Methods: The proliferative activity of hepatocellular carcinoma (HepG2) and normal human liver (THLE3) cells treated with C. roseus‑AgNPs were measured using MTT assay. The RNA samples were extracted and sequenced using BGIseq500 platform. This is followed by data filtering, mapping, gene expression analysis, DEG analysis, GO analysis, and pathway analysis. Results: The mean IC50 values of C. roseus‑AgNPs on HepG2 was 4.38±1.59 µg/mL while on THLE3 cells was 800±1.55 µg/mL. Transciptomic profiling revealed an alteration of 296 genes. C. roseus‑AgNPs induced the expression of stress-associated genes such as MT, HSP and HMOX-1. Cellular signaling pathways were potentially activated through MAPK, TNF and TGF pathways that responsible for apoptosis and cell cycle arrest. The alteration of ARF6, EHD2, FGFR3, RhoA, EEA1, VPS28, VPS25, TSG101 indicated the uptake of C. roseus-AgNPs via both clathrin-dependent and clathrin-independent endocytosis. Conclusions: This study provides the new insights on gene expression study of biosynthesized AgNPs on cancer cells. The cytotoxicity effect is mediated by the aberrant gene alteration, and more interestingly the unique selective antiproliferative properties indicates the C. roseus‑AgNPs as an ideal anticancer candidate.

The role of HNF4A in GATA4-deficiency phenotypes of hepatocellular carcinoma.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 284-284
Author(s):  
Yu Bin Tan ◽  
Timothy Shuen ◽  
Han Chong Toh
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Correlation Analysis ◽  
Cell Cycle Arrest ◽  
Cell Line ◽  
Transgenic Mouse ◽  
Cell Lines ◽  
Downstream Target ◽  
Cycle Arrest

284 Background: Hepatocellular carcinoma (HCC) is the 2nd leading global cause of cancer death. Recently, we have discovered previously undescribed deletion and germline mutation of GATA4 and showed that GATA4 is a key differentiation driver and metabolic regulator in HCC. However, as GATA4 is mostly deleted in HCC, targeting GATA4-downstream molecules is ideal. In this study, proof-of-concept experiments were conducted to show that introduction of HNF4A, which is a GATA4-regulated downstream target, could partially rescue the impaired phenotypes in GATA4-deficient HCC cell line. Methods: Correlation analysis using gene expression microarray of human HCC samples was conducted to identify the genes that are positively correlated with GATA4. A transgenic mouse model with a liver-specific conditional GATA4 knockout was designed to identify liver morphology and gene expression changes which are correlated with the loss of Gata4 in the mouse liver. CRISPR-mediated knockout of GATA4 and lentiviral HNF4A overexpression was carried out in a GATA4-deficient HCC cell lines, PLC/PRF/5 and Hep3B, followed by proliferation, apoptosis, cell cycle and senescence functional assays. Results: Pearson correlation analysis from human HCC samples showed that expression of HNF4A is positively correlated with that of GATA4. Livers from conditional Gata4 knockout mice had lower Hnf4a gene expression when compared to age-matched control mice. Loss of function analysis by CRISPR-mediated GATA4 knockout further showed downregulation of HNF4A in GATA4-deficient PLC/PRF/5 cell line. Lentiviral HNF4A overexpression in PLC/PRF/5 and Hep3B demonstrated reduced proliferation and increased apoptosis while PLC/PRF/5 also showed cell cycle arrest at G2/M phase when compared to control. However, no senescence induction was detected in HNF4A-overexpressing cells. Conclusions: Transgenic mouse data, CRISPR-mediated knockout and analysis of HCC samples showed that HNF4A is a key GATA4-downstream target. HNF4A overexpression decreases proliferation, increases apoptosis and cell cycle arrest in GATA4-deficient HCC cell lines, thus representing a possible therapeutic target for HCC.

Comprehensive Gene Expression Profile of a Normal Human Liver

2000 ◽  
Vol 269 (1) ◽  
pp. 110-116 ◽  
Author(s):  
Taro Yamashita ◽  
Shin-ichi Hashimoto ◽  
Shuichi Kaneko ◽  
Shigenori Nagai ◽  
Nobuaki Toyoda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Human Liver ◽  
Normal Human Liver ◽  
Normal Human

Monokine gene expression in normal human liver: selective involvement of the portal compartment

2008 ◽  
Vol 12 (1) ◽  
pp. 34-41 ◽  
Author(s):  
Dominique Emilie ◽  
Emmanuelle Navratil ◽  
Odile Devergne ◽  
Michel Reynes ◽  
Marie-Claude Crevon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Normal Human Liver ◽  
Normal Human

MicroRNA-1271-5p inhibits cell proliferation and enhances radiosensitivity by targeting CDK1 in hepatocellular carcinoma

2019 ◽  
Vol 167 (5) ◽  
pp. 513-524 ◽  
Author(s):  
Hong-Mei Liu ◽  
Hua-Yan Tan ◽  
Yue Lin ◽  
Bei-Ning Xu ◽  
Wen-Hua Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Cell Cycle Distribution ◽  
Cyclin Dependent Kinase ◽  
Human Liver Cell ◽  
Direct Target Gene ◽  
Normal Human Liver ◽  
Normal Human

Abstract This study aims to determine whether miR-1271-5p inhibits cell proliferation and enhances the radiosensitivity by targeting cyclin-dependent kinase 1 (CDK1) in hepatocellular carcinoma (HCC). Its expression levels in the HCC cell lines were significantly lower than those in normal human liver cell line. Bioinformatics analysis indicated CDK1 was a potential target of miR-1271-5p. Dual-Luciferase Reporter Assay confirmed that CDK1 is a direct target gene of miR-1271-5p. With overexpression of miR-1271-5p in SMMC-7721 and HuH-7 cells, cell proliferation was decreased, radiosensitivity was enhanced, cell cycle distribution was altered and the growth of transplanted tumours in nude mice was significantly reduced. miR-1271-5p overexpression enhanced radiosensitivity, which could be reduced by CDK1 overexpression. Overall, our findings suggested that miR-1271-5p inhibits cell proliferation and enhances the radiosensitivity of HCC cell lines by targeting CDK1.

Localization of CYP1A1 and CYP1A2 messenger RNA in normal human liver and in hepatocellular carcinoma byin situ hybridization

Hepatology ◽  
1991 ◽  
Vol 14 (5) ◽  
pp. 848-856 ◽  
Author(s):  
Ross A. McKinnon ◽  
Pauline de la M. Hall ◽  
Linda C. Quattrochi ◽  
Robert H. Tukey ◽  
Michael E. McManus
Keyword(s):  
Hepatocellular Carcinoma ◽  
Messenger Rna ◽  
Human Liver ◽  
Normal Human Liver ◽  
Normal Human

scholarly journals TCA Cycle Rewiring as Emerging Metabolic Signature of Hepatocellular Carcinoma

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 68 ◽  
Author(s):  
Simona Todisco ◽  
Paolo Convertini ◽  
Vito Iacobazzi ◽  
Vittoria Infantino
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Tca Cycle ◽  
Redox Balance ◽  
Metabolic Reprogramming ◽  
Glutamine Metabolism ◽  
Aberrant Gene Expression ◽  
The Tca Cycle ◽  
Aberrant Gene

Hepatocellular carcinoma (HCC) is a common malignancy. Despite progress in treatment, HCC is still one of the most lethal cancers. Therefore, deepening molecular mechanisms underlying HCC pathogenesis and development is required to uncover new therapeutic strategies. Metabolic reprogramming is emerging as a critical player in promoting tumor survival and proliferation to sustain increased metabolic needs of cancer cells. Among the metabolic pathways, the tricarboxylic acid (TCA) cycle is a primary route for bioenergetic, biosynthetic, and redox balance requirements of cells. In recent years, a large amount of evidence has highlighted the relevance of the TCA cycle rewiring in a variety of cancers. Indeed, aberrant gene expression of several key enzymes and changes in levels of critical metabolites have been observed in many solid human tumors. In this review, we summarize the role of the TCA cycle rewiring in HCC by reporting gene expression and activity dysregulation of enzymes relating not only to the TCA cycle but also to glutamine metabolism, malate/aspartate, and citrate/pyruvate shuttles. Regarding the transcriptional regulation, we focus on the link between NF-κB-HIF1 transcriptional factors and TCA cycle reprogramming. Finally, the potential of metabolic targets for new HCC treatments has been explored.

scholarly journals Calcitonin gene expression in normal human liver

FEBS Letters ◽  
1993 ◽  
Vol 331 (1-2) ◽  
pp. 15-18 ◽  
Author(s):  
S. Bracq ◽  
M. Machairas ◽  
B. Clement ◽  
E. Pidoux ◽  
M. Andreoletti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Liver ◽  
Calcitonin Gene ◽  
Normal Human Liver ◽  
Normal Human
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