miRNA-directed regulation of VEGF in tilapia under hypoxia condition

Zhao, Yan; Zhu, Chang-Dong; Yan, Biao; Zhao, Jianmin; Wang, Zhenhua

doi:10.1016/j.bbrc.2014.10.068

Cited by 31 publications

(23 citation statements)

References 25 publications

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“…The results showed the expression of EpCAM, Ki67, and VEGFA in the control group was higher than that in the si-EpCAM treatment group. VEGFA is the marker of blood vessel formation [ 22 ]. VEGFA expression decreased indicating that EpCAM plays a role in blood vessel formation.…”

Section: Resultsmentioning

confidence: 99%

By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis

Gao

Yang

et al. 2015

Oncotarget

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Epithelial cell adhesion molecule (EpCAM) is a type I transmembrane protein that is expressed in the majority of normal epithelial tissues and is overexpressed in most epithelial cancers including breast cancer, where it plays an important role in cancer progression. However, the mechanism by which EpCAM promotes the progression of breast cancer is not understood. In this study, we found that EpCAM expression was increased in tumor tissue from breast cancer patients compared to healthy patients. Overexpression of EpCAM in breast cancer cells enhanced tumor cell growth in vitro and increased invasiveness, whereas small interfering RNA-mediated silencing of EpCAM (si-EpCAM) had the opposite effect. EpCAM knockdown led to decreased phosphorylation of Raf and ERK, suppression of malignant behavior of breast cancer cells, and inhibition of the Ras/Raf/ERK signaling pathway. Furthermore, si-EpCAM-mediated invasion and metastasis of breast carcinoma cells required the downregulation of matrix metalloproteinase-9 (MMP-9) through inhibition of this signaling pathway. In conclusion, our data show that knockdown of EpCAM can inhibition breast cancer cell growth and metastasis via inhibition of the Ras/Raf/ERK signaling pathway and MMP-9.

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Section: Resultsmentioning

confidence: 99%

By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis

Gao

Yang

et al. 2015

Oncotarget

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“…Tilapia is a hypoxia-tolerant fish known as its high adaptability and fast growth performance [38]. It can naturally deal with abrupt fluctuations in oxygen availability without having to face the danger of excessive oxidative stress [38].…”

Section: Introductionmentioning

confidence: 99%

“…It can naturally deal with abrupt fluctuations in oxygen availability without having to face the danger of excessive oxidative stress [38]. So, it represents an excellent model for hypoxia research [38]. Currently, little hypoxia related molecular data in this fish is available.…”

Section: Introductionmentioning

confidence: 99%

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Characterization and functional analysis of hypoxia-inducible factor HIF1α and its inhibitor HIF1αn in tilapia

et al. 2017

PLoS ONE

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Hypoxia is a major cause of fish morbidity and mortality in the aquatic environment. Hypoxia-inducible factors are very important modulators in the transcriptional response to hypoxic stress. In this study, we characterized and conducted functional analysis of hypoxia-inducible factor HIF1α and its inhibitor HIF1αn in Nile tilapia (Oreochromis niloticus). By cloning and Sanger sequencing, we obtained the full length cDNA sequences for HIF1α (2686bp) and HIF1αn (1308bp), respectively. The CDS of HIF1α includes 15 exons encoding 768 amino acid residues and the CDS of HIF1αn contains 8 exons encoding 354 amino acid residues. The complete CDS sequences of HIF1α and HIF1αn cloned from tilapia shared very high homology with known genes from other fishes. HIF1α show differentiated expression in different tissues (brain, heart, gill, spleen, liver) and at different hypoxia exposure times (6h, 12h, 24h). HIF1αn expression level under hypoxia is generally increased (6h, 12h, 24h) and shows extremely highly upregulation in brain tissue under hypoxia. A functional determination site analysis in the protein sequences between fish and land animals identified 21 amino acid sites in HIF1α and 2 sites in HIF1αn as significantly associated sites (α = 0.05). Phylogenetic tree-based positive selection analysis suggested 22 sites in HIF1α as positively selected sites with a p-value of at least 95% for fish lineages compared to the land animals. Our study could be important for clarifying the mechanism of fish adaptation to aquatic hypoxia environment.

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“…However, the response to hypoxia only activates a small subset of these genes in any given cell , suggesting a rather specific response to hypoxia in different tissues. Recent work has determined that the HIF transcription factors also interact with the miRNA circuitry , engaging in cross talk with other signaling pathways such as Myc or Notch . These interactions initiate secondary signaling cascades, increasing the overall complexity of the system.…”

Section: The Hypoxic Nichementioning

confidence: 99%

The hypoxic microenvironment: A determinant of cancer stem cell evolution

Carnero

Lleonart

2015

Inside the Cell

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Tumors are often viewed as unique entities with specific behaviors. However, tumors are a mixture of differentially evolved subpopulations of cells in constant Darwinian evolution, selecting the fittest clone and allowing it to outgrow the rest. As in the natural environment, the niche defines the properties the fittest clones must possess. Therefore, there can be multiple fit clones because of the various microenvironments inside a single tumor. Hypoxia is considered to be a major feature of the tumor microenvironment and is a potential contributor to the cancer stem cell (CSC) phenotype and its enhanced tumorigenicity. The acidic microenvironment around hypoxic cells is accompanied by the activation of a subset of proteases that contribute to metastasis. Because of aberrant angiogenesis and the inaccessibility of their locations, hypoxic cells are less likely to accumulate therapeutic concentrations of chemotherapeutics that can lead to therapeutic resistance. Therefore, the targeting of the hypoxic CSC niche in combination with chemotherapy may provide a promising strategy for eradicating CSCs. In this review, we examine the cancer stem cell hypothesis and its relationship to the microenvironment, specifically to hypoxia and the subsequent metabolic switch and how they shape tumor behavior.

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miRNA-directed regulation of VEGF in tilapia under hypoxia condition

Cited by 31 publications

References 25 publications

By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis

By inhibiting Ras/Raf/ERK and MMP-9, knockdown of EpCAM inhibits breast cancer cell growth and metastasis

Characterization and functional analysis of hypoxia-inducible factor HIF1α and its inhibitor HIF1αn in tilapia

The hypoxic microenvironment: A determinant of cancer stem cell evolution

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