Hypoxia Inducible Factor-1alpha (HIF-1A) plays different roles in Gallbladder Cancer and Normal Gallbladder Tissues

Wu, Youliang; Meng, Delong; You, Yexiang; Sun, Ruochuan; Fu, Min; Yan, Qiang; Zhang, Shangxin; Zheng, Fang; Bao, Ji; Li, Yongxiang

doi:10.7150/jca.46749

Cited by 2 publications

(1 citation statement)

References 44 publications

(63 reference statements)

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“…It is difficult to visually display a 17-dimensional landscape, so we take two genes or dimensions ( HIF - 1 α and COX2, two genes very crucial to IGC) to visualize the landscape clearly. In Figure 2 , the X-axis shows the expression level of hypoxia-inducible factor-1 α (HIF-1 α ), which plays the role of an ‘angiogenic switch’ in the hypoxia microenvironment in many types of tumors, including IGC ( 43 ). The Y-axis shows the expression level of Cyclooxygenase-2 (COX2), which plays a crucial role in cancer development and clinical metastasis ( 44 ).…”

Section: Resultsmentioning

confidence: 99%

Quantification of the Landscape for Revealing the Underlying Mechanism of Intestinal-Type Gastric Cancer

Wang

2022

Front. Oncol.

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Gastric cancer is a daunting disease with a tragic impact on global health. It is the fourth most common cancer and has become the second most frequent cause of cancer death in recent times. According to the Lauren classification, gastric cancer can be classified into two types: intestinal and diffuse. Intestinal-type gastric cancer (IGC) is more common in elderly people, and atrophic gastritis (AG) and intestinal metaplasia (IM) have been proven to be the main premalignant causes of intestinal-type gastric cancer. In turn, Helicobacter pylori infection has been identified as the most significant cause of AG and IM. In this study, we determine the mechanism of IGC progression and how H. pylori infection induces IGC. Through researching the relevant literature, we identified the key genes associated with gastric cancer and the specific genes associated with IGC. We then use hese genes to build up a gene regulatory network for IGC. Based on this gene regulatory network, we quantify the IGC landscape. Within this landscape, there are three stable states, which are classified as the normal, AG, and gastric cancer states. Through landscape topography, we can determine the biological features and progression process of IGC. To investigate the influence of H. pylori infection on IGC, we simulated different degrees of H. pylori infection. As the H. pylori infection becomes more serious, the landscape topography changes accordingly. A fourth state, named the intestinal metaplasia (IM) state, emerges on the landscape and is associated with a very high risk of developing gastric cancer. The emergence of this state is due to the interactions/regulations among genes. Through variations in the landscape topography, we can determine the influence of H. pylori infection on IGC. Finally, we use global sensitivity analysis to research the regulations most sensitive to IGC prevention or therapies. This study presents a new approach and a novel model with which to explore the mechanism of IGC. The simulations of different degrees of H. pylori infection can provide us with a systematic view of IGC progression. The key regulations found can give us some insight and guidance for clinical trials and experimental studies.

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Section: Resultsmentioning

confidence: 99%

Quantification of the Landscape for Revealing the Underlying Mechanism of Intestinal-Type Gastric Cancer

Wang

2022

Front. Oncol.

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HDAC8 controls hypoxia-induced conversion of sensory Schwann cells into repair cells

Hertzog,

Duman,

Bochud

et al. 2024

Preprint

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Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), react to a PNS injury by converting into repair cells that foster axonal regrowth, and then remyelinate or re-ensheath regenerated axons, thereby ensuring functional recovery. The efficiency of this mechanism depends however on the time needed for axons to regrow. Here, we show that ablation of histone deacetylase 8 (HDAC8) in SCs accelerates the regrowth of sensory axons and sensory function recovery. We found that HDAC8 is specifically expressed in sensory SCs and regulates the E3 ubiquitin ligase TRAF7, which destabilizes hypoxia-inducible factor 1-alpha (HIF1a) and counteracts the phosphorylation and upregulation of c-Jun, a major inducer of the repair SC phenotype. Our study demonstrates that this phenotype switch is regulated by different mechanisms in sensory and motor SCs and is accelerated by HDAC8 downregulation, which promotes sensory axon regeneration and sensory function recovery.

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Hypoxia Inducible Factor-1alpha (HIF-1A) plays different roles in Gallbladder Cancer and Normal Gallbladder Tissues

Cited by 2 publications

References 44 publications

Quantification of the Landscape for Revealing the Underlying Mechanism of Intestinal-Type Gastric Cancer

Quantification of the Landscape for Revealing the Underlying Mechanism of Intestinal-Type Gastric Cancer

HDAC8 controls hypoxia-induced conversion of sensory Schwann cells into repair cells

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