Bioinformatics approach to predict target genes for dysregulated microRNAs in hepatocellular carcinoma: study on a chemically-induced HCC mouse model

Vecchio, Filippo Del; Gallo, Francesco; Marco, Antinisca Di; Mastroiaco, Valentina; Caianiello, Pasquale; Zazzeroni, Francesca; Alesse, Edoardo; Tessitore, Alessandra

doi:10.1186/s12859-015-0836-1

Cited by 15 publications

(18 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most dying cells may have already been cleared by the time we collected tumors; if so, their mRNA was not captured. Alternatively, phenotypic and functional differences between grow and regress tumor cells may be caused by diverse expression of miRNAs, frequently reported to impact HCC . Our RNA‐seq data only includes mRNA, so this could not be assessed in this study.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

C3HeB/FeJ Mice mimic many aspects of gene expression and pathobiological features of human hepatocellular carcinoma

Zavadil

Herzig

Hildreth

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) remains a deadly cancer, underscoring the need for relevant preclinical models. Male C3HeB/FeJ mice model spontaneous HCC with some hepatocarcinogenesis susceptibility loci corresponding to syntenic regions of human chromosomes altered in HCC. We tested other properties of C3HeB/FeJ tumors for similarity to human HCC. C3HeB/FeJ tumors were grossly visible at 4 months of age, with prevalence and size increasing until about 11 months of age. Histologic features shared with human HCC include hepatosteatosis, tumor progression from dysplasia to poorly differentiated, vascular invasion, and trabecular, oncocytic, vacuolar, and clear cell variants. More tumor cells displayed cytoplasmic APE1 staining versus normal liver. Ultrasound effectively detected and monitored tumors, with 85.7% sensitivity. Over 5000 genes were differentially expressed based on the GSE62232 and GSE63898 human HCC datasets. Of these, 158 and 198 genes, respectively, were also differentially expressed in C3HeB/FeJ. Common cancer pathways, cell cycle, p53 signaling and other molecular aspects, were shared between human and mouse differentially expressed genes. We established eigengenes that distinguish HCC from normal liver in the C3HeB/FeJ model and a subset of human HCC. These features extend the relevance and improve the utility of the C3HeB/FeJ line for HCC studies.

show abstract

Section: Discussionmentioning

confidence: 95%

“…Alternatively, phenotypic and functional differences between grow and regress tumor cells may be caused by diverse expression of miRNAs, frequently reported to impact HCC. [43][44][45][46] Our RNA-seq data only includes mRNA, so this could not be assessed in this study.…”

Section: Discussionmentioning

confidence: 99%

C3HeB/FeJ Mice mimic many aspects of gene expression and pathobiological features of human hepatocellular carcinoma

Zavadil

Herzig

Hildreth

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…miR‐182 expression is significantly upregulated in HCC patients, and dysregulated during the transition of NAFLD to non‐alcoholic steatohepatitis (NASH)‐HCC in mice . In a chemically induced HCC mouse model, miR‐182 was overexpressed . In addition, the expression of Cited2 increased liver cell proliferation, resulting in the progression of HCC that was suppressed by miR‐182‐5p .…”

Section: Introductionmentioning

confidence: 99%

“…11 In a chemically induced HCC mouse model, miR-182 was overexpressed. 12 In addition, the expression of Cited2 increased liver cell proliferation, resulting in the progression of HCC that was suppressed by miR-182-5p. 13 In HCC, natural killer (NK)-cell cytotoxicity against HCC was also augmented by miR-182.…”

mentioning

confidence: 99%

P7TP3 inhibits tumor development, migration, invasion and adhesion of liver cancer through the Wnt/β‐catenin signaling pathway

et al. 2020

View full text Add to dashboard Cite

The effect of hepatitis C virus p7 trans‐regulated protein 3 (P7TP3) in the development of hepatocellular carcinoma (HCC) is still unknown. The present study aimed to investigate the role and mechanism of P7TP3 in HCC. P7TP3 was significantly decreased in HCC tissues when compared with corresponding liver tissues immediately around the tumor (LAT) from seven HCC patients. Fewer and smaller colonies originated from HepG2‐P7TP3 cells when compared to HepG2‐NC cells. Overexpression of P7TP3 in HepG2 cells significantly repressed the growth of HCC xenografts in nude mice. Furthermore, wound‐healing tests, Transwell assays, Matrigel Transwell assays, adhesion assays, CCK‐8 assays, flow cytometry and western blotting analysis showed that P7TP3 protein expression inhibited migration, invasion, adhesion, proliferation and cell cycle progression in HCC cell lines. Moreover, P7TP3 suppressed the activity of the Wnt/β‐catenin signaling pathway, and was restored by Wnt3a, which is an activator of the Wnt/β‐catenin signaling pathway. Consistently, β‐catenin was highly expressed by P7TP3 silencing, and restored by XAV939, an inhibitor of the Wnt/β‐catenin signaling pathway. Finally, microRNA (miR)‐182‐5p suppressed the expression of target gene P7TP3 by directly interacting with the 3′‐UTR region. Taken together, P7TP3, the direct target gene of miR‐182‐5p, inhibited HCC by regulating migration, invasion, adhesion, proliferation and cell cycle progression of liver cancer cell through the Wnt/β‐catenin signaling pathway. These findings provide strong evidence that P7TP3 functions as a new promising tumor suppressor in HCC.

show abstract

“…Also, these tools could be useful to identify specific target genes for miRNAs. 14 Bioinformatics-based tools provide detection pathways of different disorders through finding the effector genes and their regulator factors in disorder process. 15…”

Section: Introductionmentioning

confidence: 99%

Molecular study of wound healing after using biosynthesized BNC/Fe<sub>3</sub>O<sub>4</sub> nanocomposites assisted with a bioinformatics approach

Moniri¹,

Moghaddam²,

Azizi³

et al. 2018

IJN

View full text Add to dashboard Cite

BackgroundMolecular investigation of wound healing has allowed better understanding about interaction of genes and pathways involved in healing progression.ObjectivesThe aim of this study was to prepare magnetic/bacterial nanocellulose (Fe3O4/BNC) nanocomposite films as ecofriendly wound dressing in order to evaluate their physical, cytotoxicity and antimicrobial properties. The molecular study was carried out to evaluate expression of genes involved in healing of wounds after treatment with BNC/Fe3O4 films.Study design, materials, and methodsMagnetic nanoparticles were biosynthesized by using Aloe vera extract in new isolated bacterial nanocellulose (BNC) RM1. The nanocomposites were characterized using X-ray diffraction, Fourier transform infrared, and field emission scanning electron microscopy. Moreover, swelling property and metal ions release profile of the nanocomposites were investigated. The ability of nanocomposites to promote wound healing of human dermal fibroblast cells in vitro was examined. Bioinformatics databases were used to identify genes with important healing effect. Key genes which interfered with healing were studied by quantitative real time PCR.ResultsSpherical magnetic nanoparticles (15–30 nm) were formed and immobilized within the structure of BNC. The BNC/Fe3O4 was nontoxic (IC50>500 μg/mL) with excellent wound healing efficiency after 48 hours. The nanocomposites showed good antibacterial activity ranging from 6±0.2 to 13.40±0.10 mm against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa. The effective genes for the wound healing process were TGF-B1, MMP2, MMP9, Wnt4, CTNNB1, hsa-miR-29b, and hsa-miR-29c with time dependent manner. BNC/Fe3O4 has an effect on microRNA by reducing its expression and therefore causing an increase in the gene expression of other genes, which consequently resulted in wound healing.ConclusionThis eco-friendly nanocomposite with excellent healing properties can be used as an effective wound dressing for treatment of cutaneous wounds.

show abstract

Bioinformatics approach to predict target genes for dysregulated microRNAs in hepatocellular carcinoma: study on a chemically-induced HCC mouse model

Cited by 15 publications

References 53 publications

C3HeB/FeJ Mice mimic many aspects of gene expression and pathobiological features of human hepatocellular carcinoma

C3HeB/FeJ Mice mimic many aspects of gene expression and pathobiological features of human hepatocellular carcinoma

P7TP3 inhibits tumor development, migration, invasion and adhesion of liver cancer through the Wnt/β‐catenin signaling pathway

Molecular study of wound healing after using biosynthesized BNC/Fe<sub>3</sub>O<sub>4</sub> nanocomposites assisted with a bioinformatics approach

Contact Info

Product

Resources

About