Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway

Ma, Xiaomin; Guo, Pengbo; Qiu, Yumin; Mu, Kun; Zhu, Lihui; Zhao, Wei; Li, Tao; Han, Lihui

doi:10.18632/oncotarget.9154

Cited by 89 publications

(110 citation statements)

References 26 publications

(27 reference statements)

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“…In line with our data, Ma et al . (2016) showed that AIM2 was down‐regulated in 113 HCC cases recruited from North China. Patients with low expression of AIM2 had a shorter life compared to those with high AIM2 expression.…”

Section: Discussionmentioning

confidence: 99%

“…Excessive AIM2 expression inhibited cell proliferation and induced apoptosis in breast carcinoma (Chen et al ., 2006; Liu et al ., 2015b). Interestingly, AIM2 expression was elevated in chronic hepatitis B (CHB) patients (Han et al ., 2015) and decreased in HCC patients (Ma et al ., 2016). However, the clinical significance of AIM2 in HCC and the mechanism of its downregualtion have not been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Chen

Liu

et al. 2017

Molecular Oncology

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Tumor metastasis is responsible for the high mortality rates in patients with hepatocellular carcinoma (HCC). Absent in melanoma 2 (AIM2) has been implicated in inflammation and carcinogenesis, although its role in HCC metastasis remains unknown. In the present study, we show that AIM2 protein expression was noticeably reduced in HCC cell lines and clinical samples. A reduction in AIM2 was closely associated with higher serum AFP levels, vascular invasion, poor tumor differentiation, an incomplete tumor capsule and unfavorable postsurgical survival odds. In vitro studies demonstrated that AIM2 expression was modulated by hepatitis B virus X protein (HBx) at transcriptional and post‐translational levels. HBx overexpression markedly blocked the expression of AIM2 at mRNA and protein levels by enhancing the stability of Enhancer of zeste homolog 2 (EZH2). Furthermore, HBx interacted with AIM2, resulting in an increase of AIM2 degradation via ubiquitination induction. Functionally, knockdown of AIM2 enhanced cell migration, formation of cell pseudopodium, wound healing and tumor metastasis, whereas reintroduction of AIM2 attenuated these functions. The loss of AIM2 induced the activation of epithelial‐mesenchymal transition (EMT). Fibronectin 1 (FN1) was found to be a downstream effector of AIM2, with its expression reversely modulated by AIM2. Silencing of FN1 significantly halted cell migration induced by AIM2 depletion. These data demonstrate that HBx‐induced loss of AIM2 is associated with poor outcomes and facilitates HCC metastasis by triggering the EMT process. The results of the present study therefore suggest that AIM2 is a potential prognostic biomarker in hepatitis B virus‐related HCC, as well as a possible therapeutic target for tumor metastasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Chen

Liu

et al. 2017

Molecular Oncology

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“…Reconstitution of AIM2 expression in HCC cell lines had an inhibitory effect on mTOR and S6K1 phosphorylation that was reversed by caspase‐1 inhibition. Reconstitution of AIM2 expression also impaired tumor growth in a HCC xenograft model . In a different mouse model of HCC, decreased AIM2 expression led to increased number of liver tumors and lung nodules .…”

Section: Aim2 In Health and Diseasementioning

confidence: 92%

“…In liver samples from patients with HCC, AIM2 expression was decreased in cancer tissue compared to corresponding non‐cancerous samples. Moreover, AIM2 expression was negatively correlated with tumor volume, grade, and metastatic progression . In liver, hepatitis B virus X protein (HBx) has been proposed to contribute to the downregulation of AIM2 expression both at the transcription and protein levels.…”

Section: Aim2 In Health and Diseasementioning

confidence: 99%

“…Indeed, HCC patients that are HBV positive show lower AIM2 expression levels compared to HCC HBV‐negative patients . Reconstitution of HCC cell lines with AIM2 diminished their proliferation and invasiveness while further decreasing the expression of AIM2 augmented signs of disease . In this cancer type the AIM2 inflammasome was proposed to negatively impact the mTOR‐S6K1 pathway.…”

Section: Aim2 In Health and Diseasementioning

confidence: 99%

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The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Lugrin

Martinon

2017

Immunological Reviews

263

199

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Recognition of pathogens and altered self must be efficient and highly specific to orchestrate appropriate responses while limiting excessive inflammation and autoimmune reaction to normal self. AIM2 is a member of innate immune sensors that detects the presence of DNA, arguably the most conserved molecules in living organisms. However, AIM2 achieves specificity by detecting altered or mislocalized DNA molecules. It can detect damaged DNA, and the aberrant presence of DNA within the cytosolic compartment such as genomic DNA released into the cytosol upon loss of nuclear envelope integrity. AIM2 is also a key sensor of pathogens that detects the presence of foreign DNA accumulating in the cytosol during the life cycle of intracellular pathogens including viruses, bacteria, and parasites. AIM2 activation initiates the assembly of the inflammasome, an innate immune complex that leads to the activation of inflammatory caspases. This triggers the maturation and secretion of the cytokines IL-1β and IL-18. It can also initiate pyroptosis, a proinflammatory form of cell death. The AIM2 inflammasome contributes to physiological responses and diseases. It is a key player in host defenses, but its deregulation can contribute immune-linked diseases, such as autoinflammatory and autoimmune pathologies. Moreover, AIM2 may play a role in cancer development. Recent studies have shown that the detection of self-DNA species by AIM2 is an important factor that contributes to diseases associated with perturbation of cellular homeostasis. Thus, in addition of being a sensor of pathogen associated molecular patterns (PAMPs), the AIM2 inflammasome is emerging as a key guardian of cellular integrity.

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A pyroptosis‐related signature predicts prognosis and indicates immune microenvironment infiltration in glioma

Chen

et al. 2022

Cancer Medicine

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Background Glioma, the most common malignant brain tumor, leads to high recurrence rates and disabilities in patients. Pyroptosis is an inflammasomes‐induced programmed cell death in response to infection or chemotherapy. However, the role of pyroptosis in glioma has not yet been elucidated. Methods RNA‐seq data and clinical information of 660 gliomas and 847 samples were downloaded from the TCGA and CGGA, respectively. Then, data of 104 normal brain tissues was retrieved from the GTEx for differential expression analysis. Twelve pairs of peritumoral tissue and glioma samples were used for validation. Gene alteration status of differentially expressed pyroptosis‐related regulators in gliomas was detected in cBioPortal algorithm. Consensus clustering was employed to classify gliomas based on differentially expressed pyroptosis‐related regulators. Subsequently, a PS‐signature was constructed using LASSO‐congressional analysis for clinical application. The immune infiltration of glioma microenvironment (TME) was explored using ESTIMATE, CIBERSORT, and the other immune signatures. Results cBioPortal algorithm revealed alteration of these regulators was correlated to better prognosis of gliomas. Then, our study showed that pyroptosis‐related regulators can be used to sort out patients into two clusters with distinct prognostic outcome and immune status. Moreover, a PS‐signature for predicting the prognosis of glioma patients was developed based on the identified subtypes. The high PS‐score group showed more abundant inflammatory cell infiltration and stronger immune response, but with poorer prognosis of gliomas. Conclusion The findings of this study provide a therapeutic basis for future research on pyroptosis and unravel the relationship between pyroptosis and glioma prognosis. The risk signature can be utilized as a prognostic biomarker for glioma.

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Loss of AIM2 expression promotes hepatocarcinoma progression through activation of mTOR-S6K1 pathway

Cited by 89 publications

References 26 publications

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

A pyroptosis‐related signature predicts prognosis and indicates immune microenvironment infiltration in glioma

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