scholarly journals MicroRNA-21 activation of Akt via PTEN is involved in the epithelial–mesenchymal transition and malignant transformation of human keratinocytes induced by arsenite

2016 ◽  
Vol 5 (4) ◽  
pp. 1140-1147 ◽  
Author(s):  
Xiaolin Lu ◽  
Yang Liu ◽  
Fei Luo ◽  
Aihua Zhang ◽  
Xinlu Liu ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Epithelial Mesenchymal Transition ◽  
Human Keratinocytes ◽  
Mesenchymal Transition

MicroRNAs are involved in the epithelial–mesenchymal transition (EMT) and malignant transformation of cells.

scholarly journals HIF-1α Promotes Hepatocellular Carcinoma Metastasis by Regulating Angiogenesis and Epithelial-Mesenchymal Transition

2020 ◽  
Author(s):  
Min Yao ◽  
Li Wang ◽  
Xiyu Chen ◽  
Ying Chen ◽  
Jie Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Malignant Transformation ◽  
Epithelial Mesenchymal Transition ◽  
Hypoxia Inducible Factor ◽  
Medical Society ◽  
Mesenchymal Transition ◽  
Positive Correlations ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor ◽  
Hcc Cells

Abstract Background: Invasion and metastasis of hepatocellular carcinoma (HCC) still remain to be hard in medical society. However, little knowledge is known regarding the hypoxia impact in HCC with angiogenesis and epithelial-mesenchymal transition (EMT). The aims of this study were to explore the regulating roles of hypoxia-inducible factor-1α (HIF-1α) in angiogenesis and EMT of HCC. Method: The levels of HIF-1α, angiopoietin-2 (Ang-2), and vascular endothelial growth factor (VEGF) expression in a cohort of chronic liver diseases were detected by enzyme- linked immunosorbent assays, and their dynamic up-regulations were confirmed in model of rat hepatocyte malignant transformation. After HIF-1α gene transfected with specific miRNA, biological behaviors of HCC cells were analyzed by transwell or invasion assay; angiogenesis and EMT were analyzed at protein level by Western blot or at mRNA by quantitative real-time PCR. Results: The levels of circulating HIF-1α, VEGF, and Ang-2 in the HCC group (145.6 ± 32.6 μg/L, 458.9 ± 125.3 μg/L, and 42.9 ± 5.1μg/L) were significantly higher (P < 0.001) than those in the LC (79.5 ± 8.4 μg/L, 206.8 ± 56.8 μg/L, and 26.2 ± 6.1 μg/L) or the CH (60.1 ± 18.8 μg/L, 178.1 ± 85.4 μg/L, and 21.8 ± 6.9 μg/L) group, respectively. Dynamic up-regulations of HIF-1α and angiogenic factors have been confirmed by rat model with hepatocyte malignant transformation. There were closely positive correlations (P < 0.001) between them of HIF-1α and VEGF or Ang-2. After HCC cells transfected with specific HIF-1α-miRNA, the levels of HIF-1α, VEGF and Ang-2 expression were significantly down-regulated, with inhibiting infiltration or migration, blockading EMT with increasing E-cadherin and decreasing of snail, twist and vimentin. Conclusions: HIF-1α over-expression could promote the metastasis or invasion of HCC via regulating neovascularization and EMT formation.

scholarly journals Clonorchis sinensis Granulin Promotes Malignant Transformation of Hepatocyte Through EGFR-Mediated RAS/MAPK/ERK and PI3K/Akt Signaling Pathways

2021 ◽  
Vol 11 ◽  
Author(s):  
Caiqin Wang ◽  
Qing He ◽  
Yingxuan Yin ◽  
Yinjuan Wu ◽  
Xuerong Li
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Signaling Pathways ◽  
Malignant Transformation ◽  
Epithelial Mesenchymal Transition ◽  
Clonorchis Sinensis ◽  
Akt Signaling ◽  
Eukaryotic Expression ◽  
Cell Counting ◽  
Mesenchymal Transition

The biological functions of growth factor, such as granulins, have been explored in parasites, and we elucidated that Clonorchis sinensis granulin (CsGRN) promoted the metastasis of hepatocellular carcinoma in our previous study. However, it is still unclear for the malignant transformation role of CsGRN in normal human hepatocytes. In this study, by transfecting pEGFP-C1-CsGRN eukaryotic expression plasmid, a cell line with stable overexpression of CsGRN in normal hepatocyte (LO2-GRN cells) was constructed. The effects on cell proliferation were detected by carrying out cell counting kit-8 (CCK8) assay and colony formation assay. Additionally, we conducted flow cytometry analysis to determine whether the proliferation of CsGRN was due to cell cycle arrest. Subsequently, the migration ability and the invasion ability of LO2-GRN cells were evaluated through wound-healing assay and transwell assay. Meanwhile, the levels of the markers of RAS/MAPK/ERK and PI3K/Akt signaling pathways activation in LO2-GRN cells were assessed by quantitative RT-PCR and Western blot. Our results indicated that CsGRN promoted the proliferation of LO2 cells by regulating the expression of cell-cycle-related genes. Moreover, the overexpression of CsGRN regulates malignant metastasis of liver cells by inducing the upregulation of epithelial–mesenchymal transition (EMT) marker proteins. Furthermore, both mRNA and protein expression levels of p-EGFR, RAS, p-ERK, p-AKT, p-PI3K, and p-braf have been enhanced by CsGRN. These results showed that CsGRN promoted the malignant transformation of hepatocytes by regulating epidermal growth factor receptor (EGFR)-mediated RAS/MAPK/ERK and PI3K/Akt signaling pathways, which suggested that CsGRN could serve as a novel oncoprotein during Clonorchis sinensis–associated malignant transformation of hepatocytes.

scholarly journals RAC1B: A Rho GTPase with Versatile Functions in Malignant Transformation and Tumor Progression

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 21 ◽  
Author(s):  
Catharina Melzer ◽  
Ralf Hass ◽  
Hendrik Lehnert ◽  
Hendrik Ungefroren
Keyword(s):  
Tumor Progression ◽  
Malignant Transformation ◽  
Cellular Response ◽  
Cell Cycle Progression ◽  
Rho Gtpase ◽  
Epithelial Mesenchymal Transition ◽  
Biochemical Properties ◽  
Apoptosis Resistance ◽  
Comprehensive Overview ◽  
Mesenchymal Transition

RAC1B is an alternatively spliced isoform of the monomeric GTPase RAC1. It differs from RAC1 by a 19 amino acid in frame insertion, termed exon 3b, resulting in an accelerated GDP/GTP-exchange and an impaired GTP-hydrolysis. Although RAC1B has been ascribed several protumorigenic functions such as cell cycle progression and apoptosis resistance, its role in malignant transformation, and other functions driving tumor progression like epithelial-mesenchymal transition, migration/invasion and metastasis are less clear. Insertion of exon 3b endows RAC1B with specific biochemical properties that, when compared to RAC1, encompass both loss-of-functions and gain-of-functions with respect to the type of upstream activators, downstream targets, and binding partners. In its extreme, this may result in RAC1B and RAC1 acting in an antagonistic fashion in regulating a specific cellular response with RAC1B behaving as an endogenous inhibitor of RAC1. In this review, we strive to provide the reader with a comprehensive overview, rather than critical discussions, on various aspects of RAC1B biology in eukaryotic cells.

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