LHBs can elevate the expression of MDR1 through HIF-1α in patients with CHB infection: a comparative proteomic study

Li, Shiying; Yang, Yanwen; Ding, Xiangchun; Yang, Min; She, Sha; Peng, Hong; Xu, Xiaoming; Ran, Xiaoping; Li, Sanglin; Hu, Peng; Hu, Huaidong; Zhang, Dazhi; Ren, Hong

doi:10.18632/oncotarget.13941

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…Furthermore, physiological substances including steroid hormones, environmental stresses such as temperature, osmotic pressure and pH, and xenobiotics such as insecticides, heavy metal and DNA damage reagents have been shown to significantly modulate ABCB1 expression in vitro 45 . Interestingly, human pathogenic virus and virus proteins are also reported to induce ABCB1 expression 49,50 . Since bats are renowned for being a reservoir of high mortality viruses like Ebola 51 and SARS 52 , some viral proteins may induce ABCB1 expression.…”

Section: Discussionmentioning

confidence: 99%

ABCB1 protects bat cells from DNA damage induced by genotoxic compounds

Koh¹,

Itahana²,

Mendenhall³

et al. 2019

Nat Commun

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Bats are unusual mammals, with the ability to fly, and long lifespans. In addition, bats have a low incidence of cancer, but the mechanisms underlying this phenomenon remain elusive. Here we discovered that bat cells are more resistant than human and mouse cells to DNA damage induced by genotoxic drugs. We found that bat cells accumulate less chemical than human and mouse cells, and efficient drug efflux mediated by the ABC transporter ABCB1 underlies this improved response to genotoxic reagents. Inhibition of ABCB1 triggers an accumulation of doxorubicin, DNA damage, and cell death. ABCB1 is expressed at higher levels in several cell lines and tissues derived from bats compared to humans. Furthermore, increased drug efflux and high expression of ABCB1 are conserved across multiple bat species. Our findings suggest that enhanced efflux protects bat cells from DNA damage induced by genotoxic compounds, which may contribute to their low cancer incidence.

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Section: Discussionmentioning

confidence: 99%

ABCB1 protects bat cells from DNA damage induced by genotoxic compounds

Koh¹,

Itahana²,

Mendenhall³

et al. 2019

Nat Commun

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“…Angiogenesis is thought to depend on a perfectly coordinated balance between endogenous-positive and negative regulatory factors. The investigation of HIF-1α, VEGF and Ang-2 levels in sera of patients with benign or malignant chronic liver diseases suggested that their synchronous increasing expression from normal control, chronic hepatitis, liver cirrhosis to HCC [27,28] .…”

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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“…ATP-binding cassette (ABC) transporters, such as MDR1, can pump chemotherapeutic drugs from the intracellular to extracellular regions of HCC cells to produce drug resistance. The reporter gene assay and electrophoretic mobility shift assay proved that HIF-1α is a critical factor for MDR1 gene overexpression ( 162 ); and (d) apoptosis inhibition. HIF-1α is the promoter activator of CBR1, and CBR1 overexpression induces apoptosis resistance by reducing oxidative stress associated with hypoxia, cisplatin, and doxorubicin treatment ( 163 ).…”

Section: Mechanisms Of Therapeutic Resistance In the Hcc Microenviron...mentioning

confidence: 99%

Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment

et al. 2022

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Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is the third leading cause of cancer-related mortality worldwide. Multifactorial drug resistance is regarded as the major cause of treatment failure in HCC. Accumulating evidence shows that the constituents of the tumor microenvironment (TME), including cancer-associated fibroblasts, tumor vasculature, immune cells, physical factors, cytokines, and exosomes may explain the therapeutic resistance mechanisms in HCC. In recent years, anti-angiogenic drugs and immune checkpoint inhibitors have shown satisfactory results in HCC patients. However, due to enhanced communication between the tumor and TME, the effect of heterogeneity of the microenvironment on therapeutic resistance is particularly complicated, which suggests a more challenging research direction. In addition, it has been reported that the three-dimensional (3D) organoid model derived from patient biopsies is more intuitive to fully understand the role of the TME in acquired resistance. Therefore, in this review, we have focused not only on the mechanisms and targets of therapeutic resistance related to the contents of the TME in HCC but also provide a comprehensive description of 3D models and how they contribute to the exploration of HCC therapies.

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LHBs can elevate the expression of MDR1 through HIF-1α in patients with CHB infection: a comparative proteomic study

Cited by 5 publications

References 29 publications

ABCB1 protects bat cells from DNA damage induced by genotoxic compounds

ABCB1 protects bat cells from DNA damage induced by genotoxic compounds

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

Overcoming the therapeutic resistance of hepatomas by targeting the tumor microenvironment

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