scholarly journals Phosphodiesterase 4D Depletion/Inhibition Exerts Anti-Oncogenic Properties in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2182
Author(s):  
Federica Ragusa ◽  
Nadia Panera ◽  
Silvia Cardarelli ◽  
Marco Scarsella ◽  
Marzia Bianchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Human Cancer ◽  
Specific Inhibitor ◽  
Protein Activity ◽  
Over Expression ◽  
Insulin Growth Factor ◽  
Cancer Types ◽  
Phosphodiesterase 4D ◽  
Hcc Cells

Isoform D of type 4 phosphodiesterase (PDE4D) has recently been associated with several human cancer types with the exception of human hepatocellular carcinoma (HCC). Here we explored the role of PDE4D in HCC. We found that PDE4D gene/protein were over-expressed in different samples of human HCCs compared to normal livers. Accordingly, HCC cells showed higher PDE4D activity than non-tumorigenic cells, accompanied by over-expression of the PDE4D isoform. Silencing of PDE4D gene and pharmacological inhibition of protein activity by the specific inhibitor Gebr-7b reduced cell proliferation and increased apoptosis in HCC cells, with a decreased fraction of cells in S phase and a differential modulation of key regulators of cell cycle and apoptosis. PDE4D silencing/inhibition also affected the gene expression of several cancer-related genes, such as the pro-oncogenic insulin growth factor (IGF2), which is down-regulated. Finally, gene expression data, available in the CancerLivER data base, confirm that PDE4D over-expression in human HCCs correlated with an increased expression of IGF2, suggesting a new possible molecular network that requires further investigations. In conclusion, intracellular depletion/inhibition of PDE4D prevents the growth of HCC cells, displaying anti-oncogenic effects. PDE4D may thus represent a new biomarker for diagnosis and a potential adjuvant target for HCC therapy.

Study of the antineoplastic effect of modulating apoptosis-related noncoding RNA in human hepatocellular carcinoma cell line (HepG2)

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mai Abdel Azeem Sherif ◽  
Emtiaz Abd-elkawy Ismail ◽  
Samar Kamal Kassim ◽  
Hanan Hussein Shehata ◽  
Marwa Ali Abdel Khalek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Noncoding Rna ◽  
Caspase 3 ◽  
Control Group ◽  
Antineoplastic Effect ◽  
And Control ◽  
Hcc Cells ◽  
Liver Tissues

Abstract MiR-421 is considered an important molecule that can prevent tumor growth. Bioinformatics analysis indicated that mRNA caspase-3 gene is a target gene of miR-421. The current study aimed to explore the functional role of miR-421 in hepatocellular carcinoma (HCC) and explore the interaction between miR-421 and caspase-3. To validate bioinformatics data, RT-qPCR was used to detect the expression of miR-421 and caspase-3 in 10 HCC tissues. The results showed miR-421 expression was significantly higher in HCC than non HCC liver tissues (P<0.01), nevertheless caspase-3 gene expression was markedly lower in HCC than non HCC liver tissues (P<0.01). Besides, miR-421 expression was negatively associated with caspase-3 expression. MiR-421 mimic and inhibitor was transfected into HCC cell lines (HepG2). Proliferation assay, showed that low-expression of miR-421 inhibited the proliferation of HCC cells. RT-qPCR was worked for detection the expression levels of miR-421 and caspase-3 in HepG2 cells before and after transfection. The results showed that miR-421 expression in HepG2 cells was significantly lower in miR-421 inhibitor transfected group than in mimic- transfected and control groups (Mock) (P≤ 0.05), and caspase-3 gene expression in HCC tissues was markedly higher in inhibitor transfected group than those transfected by mimic and control group (Mock) (P≤0.05). Thus, miR-421 inhibitor may inhibit the proliferation of HCC cells via over- expression of caspase-3.

scholarly journals BRB-ArrayTools Data Archive for Human Cancer Gene Expression: A Unique and Efficient Data Sharing Resource

2008 ◽  
Vol 6 ◽  
pp. CIN.S448 ◽  
Author(s):  
Yingdong Zhao ◽  
Richard Simon
Keyword(s):  
Gene Expression ◽  
Microarray Data ◽  
Human Cancer ◽  
Data Archive ◽  
Cancer Gene ◽  
Expression Array ◽  
Smooth Interface ◽  
Efficient Data ◽  
Potential Benefits ◽  
Cancer Types

The explosion of available microarray data on human cancer increases the urgency for developing methods for effectively sharing this data among clinical cancer investigators. Lack of a smooth interface between the databases and statistical analysis tools limits the potential benefits of sharing the publicly available microarray data. To facilitate the efficient sharing and use of publicly available microarray data among cancer investigators, we have built a BRB-ArrayTools Data Archive including over one hundred human cancer microarray projects for 28 cancer types. Expression array data and clinical descriptors have been imported into BRB-ArrayTools and are stored as BRB-ArrayTools project folders on the archive. The data archive can be accessed from: http://www.linus.nci.nih.gov/~brb/DataArchive.html Our BRB-ArrayTools data archive and GEO importer represent ongoing efforts to provide effective tools for efficiently sharing and utilizing human cancer microarray data.

scholarly journals MiR-505 suppressed the growth of hepatocellular carcinoma cells via targeting IGF-1R

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Liang Ren ◽  
Yongshan Yao ◽  
Yang Wang ◽  
Shengqiang Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Growth Factor Receptor ◽  
Mechanism Study ◽  
Down Regulation ◽  
Critical Function ◽  
Insulin Growth Factor ◽  
Huh7 Cells ◽  
Hcc Cells

Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers globally. An increasing body of evidence has demonstrated the critical function of microRNAs (miRNAs) in the initiation and progression of human cancers. Here, we showed that miR-505 was down-regulated in HCC tissues and cell lines. Reduced expression of miR-505 was significantly correlated with the worse prognosis of HCC patients. Overexpression of miR-505 suppressed the proliferation, colony formation and induced apoptosis of both HepG2 and Huh7 cells. Further mechanism study uncovered that miR-505 bound the 3′-untranslated region (3′-UTR) of the insulin growth factor receptor (IGF-1R) and inhibited the expression of IGF-1R in HCC cells. The down-regulation of IGF-1R by miR-505 further suppressed the phosphorylation of AKT at the amino acid S473. Consistently, the abundance of glucose transporter (GLUT) 1 (GLUT1) was reduced with the overexpression of miR-505. Down-regulation of GLUT1 by miR-505 consequently attenuated the glucose uptake, lactate production and ATP generation of HCC cells. Collectively, our results demonstrated the tumor suppressive function of miR-505 possibly via inhibiting the glycolysis of HCC cells. These findings suggested miR-505 as an interesting target for designing anti-cancer strategy in HCC.

scholarly journals Integrative Pan-Cancer Analysis Reveals Decreased Melatonergic Gene Expression in Carcinogenesis and RORA as a Prognostic Marker for Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Zou ◽  
Huaqin Sun ◽  
Yating Guo ◽  
Yidan Shi ◽  
Zhiyu Jiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Prognostic Marker ◽  
Nuclear Receptor ◽  
Expression Patterns ◽  
Cancer Development ◽  
Metabolic Genes ◽  
Intracellular Receptor ◽  
Cancer Types ◽  
The Relationship

BackgroundMelatonin has been shown to play a protective role in the development and progression of cancer. However, the relationship between alterations in the melatonergic microenvironment and cancer development has remained unclear.MethodsWe performed a comprehensive investigation on 12 melatonergic genes and their relevance to cancer occurrence, progression and survival by integrating multi-omics data from microarray analysis and RNA sequencing across 11 cancer types. Specifically, the 12 melatonergic genes that we investigated, which reflect the melatonergic microenvironment, included three membrane receptor genes, three nuclear receptor genes, two intracellular receptor genes, one synthetic gene, and three metabolic genes.ResultsWidely coherent underexpression of nuclear receptor genes, intracellular receptor genes, and metabolic genes was observed in cancerous samples from multiple cancer types compared to that in normal samples. Furthermore, genomic and/or epigenetic alterations partially contributed to these abnormal expression patterns in cancerous samples. Moreover, the majority of melatonergic genes had significant prognostic effects in predicting overall survival. Nevertheless, few corresponding alterations in expression were observed during cancer progression, and alterations in expression patterns varied greatly across cancer types. However, the association of melatonergic genes with one specific cancer type, hepatocellular carcinoma, identified RORA as a tumor suppressor and a prognostic marker for patients with hepatocellular carcinoma.ConclusionsOverall, our study revealed decreased melatonergic gene expression in various cancers, which may help to better elucidate the relationship between melatonin and cancer development. Taken together, our findings highlight the potential prognostic significance of melatonergic genes in various cancers.

scholarly journals Prognostic significance of FAM83D gene expression across human cancer types

Oncotarget ◽  
2015 ◽  
Vol 7 (3) ◽  
pp. 3332-3340 ◽  
Author(s):  
Peter J. Walian ◽  
Bo Hang ◽  
Jian-Hua Mao
Keyword(s):  
Gene Expression ◽  
Human Cancer ◽  
Prognostic Significance ◽  
Cancer Types

scholarly journals Chromenopyrimidinone Controls Stemness and Malignancy by suppressing CD133 Expression in Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1193 ◽  
Author(s):  
Yeonhwa Song ◽  
Sanghwa Kim ◽  
Hyeryon Lee ◽  
Joo Hwan No ◽  
Hyung Chul Ryu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Human Cancer ◽  
Point Mutations ◽  
Cd133 Expression ◽  
Control Tumor ◽  
Induced Apoptosis ◽  
Tumor Maintenance ◽  
Hcc Cells

Hepatocellular carcinoma (HCC) is a highly malignant human cancer that has increasing mortality rates worldwide. Because CD133+ cells control tumor maintenance and progression, compounds that target CD133+ cancer cells could be effective in combating HCC. We found that the administration of chromenopyrimidinone (CPO) significantly decreased spheroid formation and the number of CD133+ cells in mixed HCC cell populations. CPO not only significantly inhibited cell proliferation in HCC cells exhibiting different CD133 expression levels, but also effectively induced apoptosis and increased the expression of LC3-II in HCC cells. CPO also exhibits in vivo therapeutic efficiency in HCC. Specifically, CPO suppressed the expression of CD133 by altering the subcellular localization of CD133 from the membrane to lysosomes in CD133+ HCC cells. Moreover, CPO treatment induced point mutations in the ADRB1, APOB, EGR2, and UBE2C genes and inhibited the expression of these proteins in HCC and the expression of UBE2C is particularly controlled by CD133 expression among those four proteins in HCC. Our results suggested that CPO may suppress stemness and malignancies in vivo and in vitro by decreasing CD133 and UBE2C expression in CD133+ HCC. Our study provides evidence that CPO could act as a novel therapeutic agent for the effective treatment of CD133+ HCC.

scholarly journals Effects of TP53 mutational status on gene expression patterns across 10 human cancer types

2014 ◽  
Vol 232 (5) ◽  
pp. 522-533 ◽  
Author(s):  
Neha Parikh ◽  
Susan Hilsenbeck ◽  
Chad J Creighton ◽  
Tajhal Dayaram ◽  
Ryan Shuck ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Cancer ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Mutational Status ◽  
Cancer Types ◽  
Tp53 Mutational Status

Three-Dimensional Macroporous Sponge for the Culture of Hepatocellular Carcinoma Patient-Derived Xenograft Organoids

2021 ◽  
pp. 247263032110006
Author(s):  
Tan Boon Toh ◽  
Zheng Liu ◽  
Hanry Yu ◽  
Eliza Li Shan Fong
Keyword(s):  
Hepatocellular Carcinoma ◽  
Three Dimensional ◽  
Epithelial Cancer ◽  
Molecular Features ◽  
Patient Derived Xenograft ◽  
Carcinoma Patient ◽  
Cancer Types ◽  
Pdx Models ◽  
Hcc Cells

This protocol focuses on the culture of cells harvested from hepatocellular carcinoma (HCC) patient-derived xenografts (PDXs) as organoids using a cellulosic macroporous sponge scaffold. Compared with many other epithelial cancer types, the viability of HCC cells directly derived from patients or PDX models is notoriously challenging to maintain in vitro. We previously developed a macroporous sponge scaffold uniquely designed to provide biochemical and mechanical cues that support the culture of normal hepatocytes as spheroids with maintained functionality. Leveraging our success using this sponge scaffold to maintain normal hepatocytes in vitro, we recently demonstrated that a similar sponge scaffold enables the maintenance of HCC PDX cells as organoids with preserved viability, molecular features, and heterogeneity.

scholarly journals Discretization of Gene Expression Data Unmasks Molecular Subgroups Recurring in Different Human Cancer Types

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0161514 ◽  
Author(s):  
Manfred Beleut ◽  
Robert Soeldner ◽  
Mark Egorov ◽  
Rolf Guenther ◽  
Silvia Dehler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Data ◽  
Human Cancer ◽  
Expression Data ◽  
Molecular Subgroups ◽  
Cancer Types

scholarly journals Transcriptomics-Based Drug Repurposing Approach Identifies Novel Drugs against Sorafenib-Resistant Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2730
Author(s):  
Kelly Regan-Fendt ◽  
Ding Li ◽  
Ryan Reyes ◽  
Lianbo Yu ◽  
Nissar A. Wani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Clinical Investigation ◽  
Gene Expression Signature ◽  
Drug Repurposing ◽  
Proof Of Concept ◽  
Novel Drugs ◽  
Huh7 Cells ◽  
Hcc Cells

Objective: Hepatocellular carcinoma (HCC) is frequently diagnosed in patients with late-stage disease who are ineligible for curative surgical therapies. The majority of patients become resistant to sorafenib, the only approved first-line therapy for advanced cancer, underscoring the need for newer, more effective drugs. The purpose of this study is to expedite identification of novel drugs against sorafenib resistant (SR)-HCC. Methods: We employed a transcriptomics-based drug repurposing method termed connectivity mapping using gene signatures from in vitro-derived SR Huh7 HCC cells. For proof of concept validation, we focused on drugs that were FDA-approved or under clinical investigation and prioritized two anti-neoplastic agents (dasatinib and fostamatinib) with targets associated with HCC. We also prospectively validated predicted gene expression changes in drug-treated SR Huh7 cells as well as identified and validated the targets of Fostamatinib in HCC. Results: Dasatinib specifically reduced the viability of SR-HCC cells that correlated with up-regulated activity of SRC family kinases, its targets, in our SR-HCC model. However, fostamatinib was able to inhibit both parental and SR HCC cells in vitro and in xenograft models. Ingenuity pathway analysis of fostamatinib gene expression signature from LINCS predicted JAK/STAT, PI3K/AKT, ERK/MAPK pathways as potential targets of fostamatinib that were validated by Western blot analysis. Fostamatinib treatment reversed the expression of genes that were deregulated in SR HCC. Conclusion: We provide proof of concept evidence for the validity of this drug repurposing approach for SR-HCC with implications for personalized medicine.

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