hif 1 α inhibitor yc 1  (MedChemExpress)

Journal: Analytical Cellular Pathology (Amsterdam)

Article Title: Interleukin-6 and Hypoxia Synergistically Promote EMT-Mediated Invasion in Epithelial Ovarian Cancer via the IL-6/STAT3/HIF-1 α Feedback Loop

doi: 10.1155/2023/8334881

Figure Lengend Snippet: The IL-6/STAT3/HIF-1 α loop mediates IL-6-induction EMT in EOC. (a) Correlation between the generic EMT score and gene expression of each molecule in the signaling loop. Scatter plots showed EMT signature scores and normalized mRNA levels of 489 EOC samples based on TCGA dataset. Spearman's rank correlation analysis. (b) Blocking STAT3 and HIF-1 α with corresponding inhibitors (AG490 inhibits STAT3 and YC-1 inhibits HIF-1 α ) reversed IL-6-induced EMT in A2780, SKOV3, and A2780 clones overexpressing IL-6. Protein levels displayed are representative of three independent experiments with similar results.

Article Snippet: Pharmacological inhibitors of STAT3 (AG490) and HIF-1 α (YC-1) were purchased from Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Gene Expression, Blocking Assay, Clone Assay

Journal: Analytical Cellular Pathology (Amsterdam)

Article Title: Interleukin-6 and Hypoxia Synergistically Promote EMT-Mediated Invasion in Epithelial Ovarian Cancer via the IL-6/STAT3/HIF-1 α Feedback Loop

doi: 10.1155/2023/8334881

Figure Lengend Snippet: Schematic of the IL-6/STAT3/HIF-1 α autocrine signaling loop that mediates the interaction between IL-6 and HIF-1 α in the acquisition of EMT and invasion under hypoxic conditions. Solid lines indicate a direct action and dotted lines show an indirect action. IL-6 in the tumor microenvironment binds to its receptor and thereupon triggers the phosphorylation and nuclear localization of STAT3 by Janus kinase 2. Activated STAT3 dimers bound to specific sites in target gene promoters inducing transcription of HIF-1 α . In turn, HIF-1 α facilitates IL-6 production indirectly through proinflammatory mediators, such as NF- κ B, COX-2, or TLR4. More IL-6 is secreted out of EOC cells, further reinforcing this loop. Among these components of the loop, STAT3 and HIF-1 α have been shown to regulate the expression of EMT markers as well as EMT-related transcription factors, leading to the invasion and metastasis of EOC cells.

Article Snippet: Pharmacological inhibitors of STAT3 (AG490) and HIF-1 α (YC-1) were purchased from Cayman Chemical (Ann Arbor, MI, USA).

Techniques: Phospho-proteomics, Expressing

Journal: Journal of Immunology Research

Article Title: miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1 α /VEGFA Pathway in Hepatocellular Carcinoma

doi: 10.1155/2022/7318950

Figure Lengend Snippet: miR-138-5p is frequently downregulated in HCC tissues and HCC cell lines compared to control, and low miR-138-5p expression is associated with a high VM density and high HIF-1 α and VEGFA levels and indicates a poor prognosis in HCC patients. (a) and (b) RT–PCR analysis showed that miR-138-5p was more highly expressed in HCC tissues than in paratumour tissues. (c) RT–PCR analysis showed that miR-138-5p was expressed at lower levels in HCC cell lines than in human normal hepatocytes (MIHA cells).(d) CD31/PAS double staining was used to assess VM formation (red arrow). Immunohistochemical staining was used to assess HIF-1 α and VEGFA expression. The results showed that miR-138-5p expression was related to VM density and HIF-1 α and VEGFA levels. (e) The correlation between miR-138-5p and HIF-1 α mRNA levels in 23 HCC tissues. The Δ Ct values were subjected to Pearson correlation analysis. (f) The correlation between miR-138-5p and HIF-1 α mRNA levels in the HepG2 cell line (9 repeats). The Δ Ct values were subjected to Pearson correlation analysis. (g)–(i) The log-rank (Mantel–Cox) test showed that HCC patients with low miR-138-5p levels and high HIF-1 α and VEGFA levels demonstrated worse OS than other patients from the KM-Plotter database. Statistical significance was set as follows: ∗ represents P < 0.05, ∗∗ represents P < 0.01, and ∗∗∗ represents P < 0.001.

Article Snippet: Twenty-four hours later, the cells were transfected with the HIF-1 α inhibitor CAY10585 or transfected with a miR-138-5p mimic (Sangon Biotech, Shanghai, China) or a miR-138-5p inhibitor (Sangon Biotech, Shanghai, China) using Lipofectamine 2000 reagent (Invitrogen, Carlsbad, USA) according to the manufacturer's instructions.

Techniques: Expressing, Reverse Transcription Polymerase Chain Reaction, Double Staining, Immunohistochemical staining, Staining

Journal: Journal of Immunology Research

Article Title: miR-138-5p Inhibits Vascular Mimicry by Targeting the HIF-1 α /VEGFA Pathway in Hepatocellular Carcinoma

doi: 10.1155/2022/7318950

Figure Lengend Snippet: miR-138-5p reduces tumour cell tube formation by targeting HIF-1 α /VEGFA signalling. (a) The structure of miR-138-5p was predicted from miRTarBase ( http://mirtarbase . http://cuhk.edu.cn /). (b) The predicted binding site of miR-138-5p in the 3′-UTR of HIF-1 α and the mutated 3′-UTR of HIF-1 α . (c) A luciferase reporter plasmid containing the wild-type HIF-1 α 3′-UTR or the mutant HIF-1 α 3′-UTR was transfected into 293 T cells alone or cotransfected with the NC or miR-138-5p mimic, and luciferase activity was measured. (d) and (e) qRT–PCR detection of HIF-1 α and VEGFA mRNA expression in HCC cells treated with the miR-138-5p mimic (d) or inhibitor (e). (f) Western blot detection of HIF-1 α and VEGFA protein expression in HCC cells transfected with the miR-138-5p mimic or inhibitor or with the HIF-1 α inhibitor CAY10585 under normal oxygen and hypoxic conditions. (g) The HIF-1 α inhibitor CAY10585 reversed the effects of the miR-138-5p inhibitor on tube formation by HCC cells. Data are shown as the mean ± SD. All experiments were repeated at least 3 times. ∗ Represents P < 0.05; ∗∗ Represents P < 0.01; ∗∗∗ Represents P < 0.001.

Article Snippet: Twenty-four hours later, the cells were transfected with the HIF-1 α inhibitor CAY10585 or transfected with a miR-138-5p mimic (Sangon Biotech, Shanghai, China) or a miR-138-5p inhibitor (Sangon Biotech, Shanghai, China) using Lipofectamine 2000 reagent (Invitrogen, Carlsbad, USA) according to the manufacturer's instructions.

Techniques: Binding Assay, Luciferase, Plasmid Preparation, Mutagenesis, Transfection, Activity Assay, Quantitative RT-PCR, Expressing, Western Blot