Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis

Hu, Wei; Wang, Wei; Fang, Dan; Yin, Xiushan

doi:10.12659/msm.909290

Cited by 12 publications

(6 citation statements)

References 57 publications

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“…Previous work has identified elevated EGR1 expression as a marker for drug resistance in non-TNBC (in MCF-7 cells, which are ER+) 43 ; our results indicate that EGR1 could be a therapeutic biomarker in TNBC. It has already been identified as such in other cancers (hepatocellular carcinoma and gastric cancer 44,45 ). To develop EGR1 as a relevant target in TNBC patients, we first need to better understand its role in metastasis and CSC phenotype in future studies.…”

Section: Discussionmentioning

confidence: 95%

Differential functions of ERK1 and ERK2 in lung metastasis processes in triple-negative breast cancer

Gagliardi

Pitner

Park

et al. 2020

Sci Rep

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Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer characterized by metastasis, drug resistance and high rates of recurrence. With a lack or targeted therapies, TNBC is challenging to treat and carries a poor prognosis. Patients with TNBC tumors expressing high levels of ERK2 have a poorer prognosis than those with low ERK2-expressing tumors. The MAPK pathway is often found to be highly activated in TNBC, however the precise functions of the ERK isoforms (ERK1 and ERK2) in cancer progression have not been well defined. We hypothesized that ERK2, but not ERK1, promotes the cancer stem cell (CSC) phenotype and metastasis in TNBC. Stable knockdown clones of the ERK1 and ERK2 isoforms were generated in SUM149 and BT549 TNBC cells using shRNA lentiviral vectors. ERK2 knockdown significantly inhibited anchorage-independent colony formation and mammosphere formation, indicating compromised self-renewal capacity. This effect correlated with a reduction in migration and invasion. SCID-beige mice injected via the tail vein with ERK clones were employed to determine metastatic potential. SUM149 shERK2 cells had a significantly lower lung metastatic burden than control mice or mice injected with SUM149 shERK1 cells. The Affymetrix HGU133plus2 microarray platform was employed to identify gene expression changes in ERK isoform knockdown clones. Comparison of gene expression levels between SUM149 cells with ERK2 or ERK1 knockdown revealed differential and in some cases opposite effects on mRNA expression levels. Those changes associated with ERK2 knockdown predominantly altered regulation of CSCs and metastasis. Our findings indicate that ERK2 promotes metastasis and the CSC phenotype in TNBC.

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Section: Discussionmentioning

confidence: 95%

Differential functions of ERK1 and ERK2 in lung metastasis processes in triple-negative breast cancer

Gagliardi

Pitner

Park

et al. 2020

Sci Rep

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“…The present study was the first investigation into the hepatocarcinogenesis potential mechanism using GSEA. Multiple previous studies also have identified hub DEGs between HCC tumor and non-tumor tissues, however, the hub DEGs identified by them were performed by the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) online tool, and the database of STRING cannot represent the tissue specificity of HCC [72][73][74]. So, the hub genes identified by STRING were not real in HCC.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma

Liao

Yang

et al. 2019

J. Cancer

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Objective: Our study is aim to explore potential key biomarkers and pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using genome-wide expression profile dataset and methods.Methods: Dataset from the GSE14520 is used as the training cohort and The Cancer Genome Atlas dataset as the validation cohort. Differentially expressed genes (DEGs) screening were performed by the limma package. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and risk score model were used for pathway and genes identification.Results: GSEA revealed that several pathways and biological processes are associated with hepatocarcinogenesis, such as the cell cycle, DNA repair, and p53 pathway. A total of 160 DEGs were identified. The enriched functions and pathways of the DEGs included toxic substance decomposition and metabolism processes, and the P450 and p53 pathways. Eleven of the DEGs were identified as hub DEGs in the WGCNA. In survival analysis of hub DEGs, high expression of PRC1 and TOP2A were significantly associated with poor clinical outcome of HBV-related HCC, and shown a good performance in HBV-related HCC diagnosis. The prognostic signature consisting of PRC1 and TOP2A also doing well in the prediction of HBV-related HCC prognosis. The diagnostic and prognostic values of PRC1 and TOP2A was confirmed in TCGA HCC patients.Conclusions: Key biomarkers and pathways identified in the present study may enhance the comprehend of the molecular mechanisms underlying hepatocarcinogenesis. Additionally, mRNA expression of PRC1 and TOP2A may serve as potential diagnostic and prognostic biomarkers for HBV-related HCC.

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“…C. Rhizoma was identified to target MYC using the TCMSP ( https://tcmsp-e.com/ ) ( Ru et al, 2014 ) and TCM-MESH ( http://mesh.tcm.microbioinformatics.org/ ) ( Zhang et al, 2017 ) databases, respectively ( Dong et al, 2019 ). Moreover, 56 upregulated and 8 downregulated genes of berberine-treated HCC (HepG2) cells were identified and enriched in cell cycle, cell apoptosis, and transcription ( Hu et al, 2018 ). Berberine could suppress cell proliferation and induce apoptosis by upregulating 1,960 genes and downregulating 4,837 genes, that are involved in cellular, metabolic, and single-organism processes in gastric cancer (SGC-7901) cells ( Yang et al, 2018 ).…”

Section: Omics Studiesmentioning

confidence: 99%

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

Chen

Liang

et al. 2022

Front. Pharmacol.

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Cancer is a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer. Coptidis Rhizoma (C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies on C. Rhizoma present significant progress on its anticancer effects and the corresponding mechanisms as well as its clinical applications. Herein, keywords related to C. Rhizoma, cancer, gastrointestinal cancer, and omics were searched in PubMed and the Web of Science databases, and more than three hundred recent publications were reviewed and discussed. C. Rhizoma extract along with its main components, berberine, palmatine, coptisine, magnoflorine, jatrorrhizine, epiberberine, oxyepiberberine, oxyberberine, dihydroberberine, columbamine, limonin, and derivatives, are reviewed. We describe novel and classic anticancer mechanisms from various perspectives of pharmacology, pharmaceutical chemistry, and pharmaceutics. Researchers have transformed the chemical structures and drug delivery systems of these components to obtain better efficacy and bioavailability of C. Rhizoma. Furthermore, C. Rhizoma in combination with other drugs and their clinical application are also summarized. Taken together, C. Rhizoma has broad prospects as a potential adjuvant candidate against cancers, making it reasonable to conduct additional preclinical studies and clinical trials in gastrointestinal cancer in the future.

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Identification of Biological Targets of Therapeutic Intervention for Hepatocellular Carcinoma by Integrated Bioinformatical Analysis

Cited by 12 publications

References 57 publications

Differential functions of ERK1 and ERK2 in lung metastasis processes in triple-negative breast cancer

Differential functions of ERK1 and ERK2 in lung metastasis processes in triple-negative breast cancer

Comprehensive investigation of key biomarkers and pathways in hepatitis B virus-related hepatocellular carcinoma

Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers

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