<i>Retracted:</i><scp>HB</scp>x‐mediated decrease of <scp>AIM</scp>2 contributes to hepatocellular carcinoma metastasis

Chen, Shi Lu; Liu, Li Li; Lu, Shi Xun; Luo, Rong; Wang, Chun Hua; Wang, Hong; Cai, Shaohang; Yang, Xia; Xie, Dan; Zhang, Chris Zhiyi; Yun, Jing Ping

doi:10.1002/1878-0261.12090

Cited by 85 publications

(93 citation statements)

References 45 publications

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“…The miR-155 seed site in ZHX2 3 0 UTR was deleted for the 3 0 UTR-del mut. [36][37][38][39][40][41] Here, we have identified HBxmediated inhibition of ZHX2 via miR-155 as another possible mechanism by which HBV influences HCC progression (Fig. The pRL-TK plasmid was transfected into all cells as Renilla luciferase control.…”

Section: Discussionmentioning

confidence: 99%

HBV suppresses ZHX2 expression to promote proliferation of HCC through miR‐155 activation

Song

Tan

et al. 2018

Intl Journal of Cancer

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Initiation of hepatocellular carcinoma (HCC) by chronic hepatitis B virus (HBV) infection is a complex process that includes both oncogene activation and tumor suppressor inhibition. The HBV X (HBx) protein has an important and complex role in processes leading to HCC. We previously identified the mammalian Zinc fingers and homeoboxes 2 (ZHX2) gene as an HCC-associated tumor suppressor gene. In the present study, we investigated whether the oncogenic properties of HBV and, more specifically, HBx, involved ZHX2 silencing. Our data indicates that ZHX2 expression is significantly decreased in tumor tissues from HBV-positive HCC patients and livers from HBV transgenic mice. In vitro and in vivo studies confirmed that HBV-encoded proteins, particularly HBx, inhibits both the expression and tumor suppression properties of ZHX2. Further analyses identified miR-155, a well-known oncomiR in various cancers, as an important link between HBx and ZHX2 inhibition. Increased miR-155 levels were found in HBV-positive tumors, livers of HBV transgenic mice and HBx-overexpressing hepatoma cell lines. MiR-155 overexpression reduced ZHX2 levels via miR-155 seed sites in the ZHX2 3'UTR, whereas blocking miR-155 levels led to increased ZHX2 levels. Taken together, our data indicate that HCC-promoting properties of HBV may include ZHX2 silencing via a miR-155 dependent pathway and suggests a novel therapy for HBV-related HCC.

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Section: Discussionmentioning

confidence: 99%

HBV suppresses ZHX2 expression to promote proliferation of HCC through miR‐155 activation

Song

Tan

et al. 2018

Intl Journal of Cancer

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“…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%

“…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. 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 .…”

Section: Aim2 In Health and Diseasementioning

confidence: 99%

“…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 . AIM2 silencing increased Fibronectin 1 (FN1), a factor that could be responsible for the epithelial to mesenchymal transition enabling HCC metastasis .…”

Section: Aim2 In Health and Diseasementioning

confidence: 99%

“…In a different mouse model of HCC, decreased AIM2 expression led to increased number of liver tumors and lung nodules . AIM2 silencing increased Fibronectin 1 (FN1), a factor that could be responsible for the epithelial to mesenchymal transition enabling HCC metastasis . Whether AIM2 ability to repress FN1 depends on inflammasome assembly has not been investigated so far.…”

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

290

205

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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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Loss of RDM1 enhances hepatocellular carcinoma progression via p53 and Ras/Raf/ERK pathways

et al. 2019

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Hepatocellular carcinoma (HCC), with its ineffective therapeutic options and poor prognosis, represents a global threat. In the present study, we show that RAD52 motif 1 (RDM1), a key regulator of DNA doublestrand break repair and recombination, is downregulated in HCC tissues and suppresses tumor growth. In clinical HCC samples, low expression of RDM1 correlates with larger tumor size, poor tumor differentiation, and unfavorable survival. In vitro and in vivo data demonstrate that knockdown of RDM1 increases HCC cell proliferation, colony formation, and cell population at G2/M phase, whereas RDM1 overexpression results in the opposite phenotypes. Mechanistically, RDM1 binds to the tumor suppressor p53 and enhances its protein stability. In the presence of p53, RDM1 suppresses the phosphorylation of Raf and ERK. Overexpression of p53 or treatment with ERK inhibitor significantly abolishes cell proliferation induced by the depletion of RDM1. In addition, overexpression of methyltransferase-like 3 markedly induces N6-methyladenosine modification of RDM1 mRNA and represses its expression. Taken together, our study indicates that RDM1 functions as a tumor suppressor and may be a potential prognostic and therapeutic factor for HCC.

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

Cited by 85 publications

References 45 publications

HBV suppresses ZHX2 expression to promote proliferation of HCC through miR‐155 activation

HBV suppresses ZHX2 expression to promote proliferation of HCC through miR‐155 activation

The AIM2 inflammasome: Sensor of pathogens and cellular perturbations

Loss of RDM1 enhances hepatocellular carcinoma progression via p53 and Ras/Raf/ERK pathways

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