Bclaf1 promotes angiogenesis by regulating HIF-1α transcription in hepatocellular carcinoma

Wen, Ying; Zhou, Xueqiong; Lu, Meiting; He, Miao; Tian, Ye; Liu, Lixia; Wang, Mengnan; Tan, Wenchong; Deng, Yaotang; Yang, Xushan; Mayer, Matthias P.; Zou, Fei; Chen, Xuemei

doi:10.1038/s41388-018-0552-1

Cited by 78 publications

(73 citation statements)

References 44 publications

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“…A large body of data has shown that transcription factors such as heat shock factors HSF2 and HSP4 and early growth response 1 (Egr-1) upregulate Hif-1α under hypoxia (R. Chen, Liliental, Kowalski, Lu, & Cohen, 2011) (Rong et al, 2006). Moreover, regulation of Hif-1α transcription was observed in cancerous tissues; for example, in hepatocellular carcinoma (HCC), Bclaf-1 enhances transcription of Hif-1α (Wen et al, 2019). In contrast, signal transducer and activator of transcription 3 (Stat3) inhibits the oncogenic potential of HIF-1α induced by hypoxia (Niu et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process

Machcińska

Kopcewicz

Bukowska

et al. 2020

Preprint

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Hypoxia and hypoxia-regulated factors [hypoxia-inducible factor-1α (Hif-1α), factor inhibiting Hif-1α (Fih-1)] have essential roles in skin wound healing. Using Foxn1-/- mice that can heal skin injuries in a unique scar-free manner, we investigated the interaction between Foxn1 and hypoxia-regulated factors. Foxn1-/- mice displayed impairments in the regulation of Hif-1α and Fih-1 during the healing process. An analysis of wounded skin showed that the skin of Foxn1-/- mice healed in a scarless manner, displaying rapid re-epithelialization and an increase in Tgfβ-3 and collagen III expression. An in vitro analysis revealed that Foxn1 overexpression in keratinocytes isolated from the skin of Foxn1-/- mice led to reduced Hif-1α expression in normoxic but not hypoxic cultures and inhibited Fih-1 expression exclusively under hypoxic conditions. These data indicate that in the skin, Foxn1 affects hypoxia-regulated factors that control the wound healing process and suggest that under normoxic conditions, Foxn1 is a limiting factor for Hif-1α.

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Section: Discussionmentioning

confidence: 99%

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process

Machcińska

Kopcewicz

Bukowska

et al. 2020

Preprint

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“…HIF-1α overexpression was con rmed during hepatocytes malignant transformation with HCC progress, because it regulates the transcription of downstream numerous genes including angiogenesis or proliferation to set basis for HCC growth and metastasis [31,32] . However, the speci c miRNA decreased HIF-1α expression and suppressed angiogenesis in the HCC cell lines by down-regulating VEGF and Ang-2, indicated that HIF-1α regulate the angiogenesis of HCC [33] .…”

Section: Discussionmentioning

confidence: 99%

HIF-1α promotes hepatocellular carcinoma metastasis by regulating angiogenesis and epithelial-mesenchymal transition

Yao

Wang

Chen

et al. 2020

Preprint

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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. Methods 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 ± 5.1 µg/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 These data have highlighted the HIF-1α over-expression could promote the metastasis or invasion of HCC via regulating neovascularization and EMT formation.

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“…EPO and VEGF are downstream genes of HIF-1α that regulate and change physiological functions 29 , 30 . In this study, we found that the expression level of HIF-1α was increased, and the expression levels of EPO and VEGF were also increased.…”

Section: Discussionmentioning

confidence: 99%

Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea–hypopnea syndrome rabbits

Zhu

Kang

Zhang

et al. 2020

Sci Rep

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All methods in this study were performed in accordance with the medical ethics committee in Hospital of Stomatology, Hebei Medical University. Animal use and care was in accordance with the guidelines of the medical ethics committee for the housing and care of animals bred, supplied and used for scientific purposes. All experiments were performed in accordance with relevant guidelines and regulations. The work was approved by the medical ethics committee in Hospital of Stomatology, Hebei Medical University (Certificate No. [2017]016). Animal model development. Every effort was made to minimize animal pain and suffering. A total of 18 male 6-month-old New Zealand white rabbits (initial weight, 3-3.5 kg) were randomly divided into three groups: the OSHAS, MAD, and control groups, with 6 rabbits in each group. All of the animals were housed under normal laboratory conditions. Food and water were available ad libitum. The animal models were developed in the same way as in our previous studies 12,13. Briefly, OSAHS was induced via injection of gel into the submucous muscular layer in the centre of the soft palate 1.5 cm away from the junction of the soft and hard palate (Fig. 1). No gel was injected in the control group. Animals in these two groups were later confirmed to have OSAHS by clinical signs, CBCT scanning and polysomnography (PSG).

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Bclaf1 promotes angiogenesis by regulating HIF-1α transcription in hepatocellular carcinoma

Cited by 78 publications

References 44 publications

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process

HIF-1α promotes hepatocellular carcinoma metastasis by regulating angiogenesis and epithelial-mesenchymal transition

Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea–hypopnea syndrome rabbits

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Bclaf1 promotes angiogenesis by regulating HIF-1α transcription in hepatocellular carcinoma

Cited by 78 publications

References 44 publications

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1−/−) mice affects the skin wound healing process

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1−/−) mice affects the skin wound healing process

HIF-1α promotes hepatocellular carcinoma metastasis by regulating angiogenesis and epithelial-mesenchymal transition

Effect of mandibular advancement device treatment on HIF-1α, EPO and VEGF in the myocardium of obstructive sleep apnea–hypopnea syndrome rabbits

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Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process

Impairment of the Hif-1α regulatory pathway in Foxn1-deficient (Foxn1^−/−) mice affects the skin wound healing process