N-methyl-N-nitro-N-nitrosoguanidine-mediated ING4 downregulation contributed to the angiogenesis of transformed human gastric epithelial cells

Chen, Yansu; Fu, Rui; Xu, Mengdie; Huang, Yefei; Sun, Guochen; Xu, Li‐Chun

doi:10.1016/j.lfs.2018.02.034

Cited by 12 publications

(5 citation statements)

References 29 publications

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“…CM collected from ING4‐overexpressing ARPE‐19 cells could efficiently protect HRECs against hypoxic injuries by maintaining tube formation capacity, indicating that ING4 had a protective effect on endothelial cells. Our findings are in line with a previous study indicating that ING4 plays a suppressive role in angiogenesis in many disease models (Chen et al, ; Yansu et al, ), thus allowing us to highlight ING4′s vasculoprotective properties in DR.…”

Section: Discussionsupporting

confidence: 92%

“…CM collected from ING4-overexpressing ARPE-19 cells could efficiently protect HRECs against hypoxic injuries by maintaining tube formation capacity, indicating that ING4 had a protective effect on endothelial cells. Our findings are in line with a previous study indicating that ING4 plays a suppressive role in angiogenesis in many disease models(Chen et al, 2016;Yansu et al, 2018), thus allowing us to highlight ING4′s vasculoprotective properties in DR. To gain further insight into the molecular mechanisms through which ING4 inhibits migration and angiogenic paracrine ability in RPE cells, we examined intracellular signaling pathways. Previous studies have indicated that knocking down Sp1 in various cell lines inhibits cell migration and angiogenesis.…”

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confidence: 92%

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Inhibitor of growth 4 affects hypoxia‐induced migration and angiogenesis regulation in retinal pigment epithelial cells

Yang

Gong

et al. 2019

Journal Cellular Physiology

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Inhibitor of growth 4 (ING4), a potential tumor suppressor, is implicated in cell migration and angiogenesis. However, its effects on diabetic retinopathy (DR) have not been elucidated. In this study, we aimed to evaluate ING4 expression in normal and diabetic rats and clarify its effects on hypoxia‐induced dysfunction in human retinal pigment epithelial (ARPE‐19) cells. A Type 1 diabetic model was generated by injecting rats intraperitoneally with streptozotocin and then killed them 4, 8, or 12 weeks later. ING4 expression in retinal tissue was detected using western blot analysis, reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR), and immunohistochemistry assays. After transfection with an ING4 overexpression lentiviral vector or small interfering RNA (siRNA), ARPE‐19 migration under hypoxia was tested using wound healing and transwell assays. The angiogenic effect of conditioned medium (CM) from ARPE‐19 cells was examined by assessing human retinal endothelial cell (HREC) capillary tube formation. Additionally, western blot analysis and RT‐qPCR were performed to investigate the signaling pathways in which ING4, specificity protein 1 (Sp1), matrix metalloproteinase 2 (MMP‐2), MMP‐9, and vascular endothelial growth factor A (VEGF‐A) were involved. Here, we found that ING4 expression was significantly reduced in the diabetic rats’ retinal tissue. Silencing ING4 aggravated hypoxia‐induced ARPE‐19 cell migration. CM collected from ING4 siRNA‐transfected ARPE‐19 cells under hypoxia promoted HREC angiogenesis. These effects were reversed by ING4 overexpression. Furthermore, ING4 suppressed MMP‐2, MMP‐9, and VEGF‐A expression in an Sp1‐dependent manner in hypoxia‐conditioned ARPE‐19 cells. Overall, our results provide valuable mechanistic insights into the protective effects of ING4 on hypoxia‐induced migration and angiogenesis regulation in ARPE‐19 cells. Restoring ING4 may be a novel strategy for treating DR.

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Section: Discussionsupporting

confidence: 92%

supporting

confidence: 92%

Inhibitor of growth 4 affects hypoxia‐induced migration and angiogenesis regulation in retinal pigment epithelial cells

Yang

Gong

et al. 2019

Journal Cellular Physiology

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“…Cancer gene therapy represents a new and promising therapeutic modality for various types of cancer. Inhibitor of growth 4 (ING4), an intracellular tumor growth inhibitor, may significantly suppress tumor growth via the induction of cell cycle alterations, apoptosis and the inhibition of tumor angiogenesis 5,6. Interleukin-24 (IL-24), also known as melanoma differentiation-associated gene-7, is a secreted cytokine and membrane receptor-mediated tumor growth suppressor 7.…”

Section: Introductionmentioning

confidence: 99%

<p>Cationic <em>Antheraea pernyi</em> Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells</p>

Qu¹,

Wang²,

Feng³

et al. 2019

IJN

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IntroductionCancer gene therapy requires both effective tumor suppressor genes and safe vectors that express target genes efficiently. Inhibitor of growth 4 (ING4) inhibits tumor growth via multiple pathways. Interleukin-24 (IL-24) also has tumor-suppressive activity against a broad spectrum of human cancers. Adenovirus (Ad) vectors exhibit high infection efficiency, but potential toxicity related to high doses of adenovirus has led to careful reconsideration of their use in human clinical trials. Antheraea pernyi silk fibroin (ASF) is a cytocompatible and biodegradable natural polymer, and it possesses Arg–Gly–Asp sequences exhibiting a high binding affinity and selectivity for αvβ3 and αvβ5 integrin receptors, which are overexpressed in tumor vessels and most tumor cells.MethodsIn this study, an Arg-Gly-Asp peptide-modified Ad vector coexpressing ING4 and IL-24 was constructed by homologous recombination of the dual gene coexpression transfer plasmid and RGD-modified pAdEasy-1 adenoviral backbone plasmid. The cationic ASF (CASF) was prepared by modifying ASF with low-molecular-weight PEI. The negatively charged Ad vector was modified with CASF to form a CASF/Ad complex.ResultsHuman hepatoma carcinoma SMMC-7721 cells and normal hepatic L-02 cells were infected with the CASF/Ad complex, which showed significantly higher infection efficiency than the naked Ad. The CASF/Ad complex could effectively mediate the expression of the target gene ING4 in SMMC-7721 cells and the secretion of the target gene IL-24 from SMMC-7721 cells, thus inducing apoptosis of hepatoma carcinoma SMMC-7721 cells. The viability of SMMC-7721 and L-02 cells infected with the CASF/Ad complex was further assessed, and it was found that the growth of SMMC-7721 cells was significantly inhibited but that the growth and proliferation of L-02 cells were not affected.ConclusionThe CASF/Ad complex constructed in this study, showing improved infection efficiency and enhanced suppressive effects on human hepatoma carcinoma SMMC-7721 cells, has the potential to reduce the dose of adenovirus and still maintain high infection efficiency and tumor inhibition.

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“…Some ING proteins were reported to hamper angiogenesis, migration, and invasion capacity of malignant cells [17,24,[40][41][42][43]. ING3 protects PC cells from metastasis-associated epithelial-mesenchymal transition (EMT) characterised by decreased protein expression of epithelial marker E-Cadherin and upregulated expression of mesenchymal markers N-Cadherin and Vimentin [39,44,45].…”

Section: Ing Factors Regulate Emtmentioning

confidence: 99%

ING Tumour Suppressors and ING Splice Variants as Coregulators of the Androgen Receptor Signalling in Prostate Cancer

Melekhova

Baniahmad

2021

Cells

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Prevention and overcoming castration resistance of prostate cancer (PC) remains one of the main unsolved problems in modern oncology. Hence, many studies are focused on the investigation of novel androgen receptor (AR) regulators that could serve as potential drug targets in disease therapy. Among such factors, inhibitor of growth (ING) proteins were identified. Some ING proteins act as AR transcriptional coregulators, indicating their relevance for PC research. The ING family consists of five protein-coding genes from ING1 to ING5 and pseudogene INGX. The ING genes were revealed through their sequence homology to the first identified ING1 from an in vivo screen. ING factors are a part of histone modification complexes. With the help of the conserved plant homeodomain (PHD) motif, ING factors bind to Histone 3 Lysine 4 (H3K4) methylation mark with a stronger affinity to the highest methylation grade H3K4me3 and recruit histone acetyltransferases (HAT) and histone deacetylases (HDAC) to chromatin. ING1 and ING2 are core subunits of mSIN3a-HDAC corepressor complexes, whereas ING3–5 interact with different HAT complexes that serve as coactivators. ING members belong to type II tumour suppressors and are frequently downregulated in many types of malignancies, including PC. As the family name indicates, ING proteins are able to inhibit cell growth and tumour development via regulation of cell cycle and cancer-relevant pathways such as apoptosis, cellular senescence, DNA repair, cell migration, invasion, and angiogenesis. Many ING splice variants that enhance the diversity of ING activity were discovered. However, it seems that the existence of multiple ING splice variants is underestimated, since alternative splice variants, such as the AR coregulators ING1 and ING3, counteract full-length ING and thus play an opposite functional role. These results open a novel prospective investigation direction in understanding ING factors biology in PC and other malignancies.

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N-methyl-N-nitro-N-nitrosoguanidine-mediated ING4 downregulation contributed to the angiogenesis of transformed human gastric epithelial cells

Cited by 12 publications

References 29 publications

Inhibitor of growth 4 affects hypoxia‐induced migration and angiogenesis regulation in retinal pigment epithelial cells

Inhibitor of growth 4 affects hypoxia‐induced migration and angiogenesis regulation in retinal pigment epithelial cells

<p>Cationic <em>Antheraea pernyi</em> Silk Fibroin-Modified Adenovirus-Mediated ING4 and IL-24 Dual Gene Coexpression Vector Suppresses the Growth of Hepatoma Carcinoma Cells</p>

ING Tumour Suppressors and ING Splice Variants as Coregulators of the Androgen Receptor Signalling in Prostate Cancer

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