<i><scp>NLRC</scp></i> and <i><scp>NLRX</scp></i> gene family <scp>mRNA</scp> expression and prognostic value in hepatocellular carcinoma

Wang, Xiangkun; Yang, Chengkun; Liao, Xiwen; Han, Chuangye; Yu, Tingdong; Huang, Ketuan; Liu, Yu; Zhu, Guangzhi; Su, Hao; Liu, Xiaoguang; Ye, Xinping; Chen, Bin; Peng, Minhao; Peng, Tao

doi:10.1002/cam4.1202

Cited by 15 publications

(10 citation statements)

References 66 publications

(77 reference statements)

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“…The NOD-like receptor signaling pathway is composed of regulating factors and receptors including NLRC and NLRX family gene members. This result parallels our previous report that NLRC and NLRX gene subfamily members are potential biomarkers for HCC 56. Hepatitis B was enriched in the results by targeting APAF1 , TICAM1 and TBK1 .…”

Section: Discussionsupporting

confidence: 90%

Clustered microRNAs hsa-miR-221-3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma

Wang¹,

Liao²,

Huang³

et al. 2019

J. Cancer

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Objective : MicroRNAs (miRNAs) have been explored in malignancies. We investigated the functions of clustered miRNAs hsa-miR-221/222-3p in hepatocellular carcinoma (HCC). Methods : Human miRNA tissue atlas website was determined expression levels in liver tissue. Four databases, TarBase, miRTarBase, miRecords and miRPathDB, were found experimentally validated target genes of clustered miRNAs. TargetScanHuman was predicted target genes. The STRING website was depicted protein-protein interaction (PPI) networks. The OncoLnc website analyzed prognostic values for hsa-miR-221/222-3p and their target genes. The MCODE plugin calculated modules of PPI networks. Receiver operating characteristic (ROC) curves were predicted 1, 3, and 5 years prognostic values. Results : Expression of clustered miRNAs was high in liver tissues. A total of 1577 target genes were identified. Enrichment analysis showed that target genes were enriched mainly in cancer, Wnt signaling and ErbB signaling pathways. Two modules were calculated using PPI networks. Has-miR-221-3p was not associated with prognosis ( P = 0.401). Has-miR-222-3p and target genes ESR1 , TMED7 , CBFB , ETS2 , UBE2J1 and UBE2N of the clustered miRNAs were associated with HCC survival (all P < 0.05). Has-miR-222-3p, CBFB , and UBE2N showed good performance of ROC in prognosis prediction at 1, 3, and 5 years (all area under curves > 0.600). Conclusion : Has-miR-222-3p and target genes , especially CBFB , UBE2N , may serve as prognostic predictors for HCC.

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Section: Discussionsupporting

confidence: 90%

Clustered microRNAs hsa-miR-221-3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma

Wang¹,

Liao²,

Huang³

et al. 2019

J. Cancer

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“…By contrast, NLRC4 expression was found to show no correlation with the survival of patients with hepatocellular carcinoma by Wang et al . 33 . Recently, Xiao-Feng et al .…”

Section: Discussionmentioning

confidence: 99%

Upregulation of the NLRC4 inflammasome contributes to poor prognosis in glioma patients

Lim

Kim

Park

et al. 2019

Sci Rep

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Inflammation in tumor microenvironments is implicated in the pathogenesis of tumor development. In particular, inflammasomes, which modulate innate immune functions, are linked to tumor growth and anticancer responses. However, the role of the NLRC4 inflammasome in gliomas remains unclear. Here, we investigated whether the upregulation of the NLRC4 inflammasome is associated with the clinical prognosis of gliomas. We analyzed the protein expression and localization of NLRC4 in glioma tissues from 11 patients by immunohistochemistry. We examined the interaction between the expression of NLRC4 and clinical prognosis via a Kaplan-Meier survival analysis. The level of NLRC4 protein was increased in brain tissues, specifically, in astrocytes, from glioma patients. NLRC4 expression was associated with a poor prognosis in glioma patients, and the upregulation of NLRC4 in astrocytomas was associated with poor survival. Furthermore, hierarchical clustering of data from the Cancer Genome Atlas dataset showed that NLRC4 was highly expressed in gliomas relative to that in a normal healthy group. Our results suggest that the upregulation of the NLRC4 inflammasome contributes to a poor prognosis for gliomas and presents a potential therapeutic target and diagnostic marker.

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“…Reduced mRNA levels of NLRC4 are evident in the tumor tissues of colorectal cancer 118 . However, more recent studies have demonstrated normal levels in lung tumors 119 and hepatocellular carcinoma, 120 along with increased expression in breast cancer and glioma 121,122 . The role of NLRC4 in tumor regulation and suppression is not always consistent even in the same tumor model (Table 4), as discussed further below.…”

Section: Nlrc4 In Cancermentioning

confidence: 96%

Molecular mechanisms activating the NAIP‐NLRC4 inflammasome: Implications in infectious disease, autoinflammation, and cancer

Kay

Wang

Kirkby

et al. 2020

Immunological Reviews

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Cytosolic innate immune sensing is a cornerstone of innate immunity in mammalian cells and provides a surveillance system for invading pathogens and endogenous danger signals. The NAIP‐NLRC4 inflammasome responds to cytosolic flagellin, and the inner rod and needle proteins of the type 3 secretion system of bacteria. This complex induces caspase‐1‐dependent proteolytic cleavage of the proinflammatory cytokines IL‐1β and IL‐18, and the pore‐forming protein gasdermin D, leading to inflammation and pyroptosis, respectively. Localized responses triggered by the NAIP‐NLRC4 inflammasome are largely protective against bacterial pathogens, owing to several mechanisms, including the release of inflammatory mediators, liberation of concealed intracellular pathogens for killing by other immune mechanisms, activation of apoptotic caspases, caspase‐7, and caspase‐8, and expulsion of an entire infected cell from the mammalian host. In contrast, aberrant activation of the NAIP‐NLRC4 inflammasome caused by de novo gain‐of‐function mutations in the gene encoding NLRC4 can lead to macrophage activation syndrome, neonatal enterocolitis, fetal thrombotic vasculopathy, familial cold autoinflammatory syndrome, and even death. Some of these clinical manifestations could be treated by therapeutics targeting inflammasome‐associated cytokines. In addition, the NAIP‐NLRC4 inflammasome has been implicated in the pathogenesis of colorectal cancer, melanoma, glioma, and breast cancer. However, no consensus has been reached on its function in the development of any cancer types. In this review, we highlight the latest advances in the activation mechanisms and structural assembly of the NAIP‐NLRC4 inflammasome, and the functions of this inflammasome in different cell types. We also describe progress toward understanding the role of the NAIP‐NLRC4 inflammasome in infectious diseases, autoinflammatory diseases, and cancer.

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NLRC and NLRX gene family mRNA expression and prognostic value in hepatocellular carcinoma

Cited by 15 publications

References 66 publications

Clustered microRNAs hsa-miR-221-3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma

Clustered microRNAs hsa-miR-221-3p/hsa-miR-222-3p and their targeted genes might be prognostic predictors for hepatocellular carcinoma

Upregulation of the NLRC4 inflammasome contributes to poor prognosis in glioma patients

Molecular mechanisms activating the NAIP‐NLRC4 inflammasome: Implications in infectious disease, autoinflammation, and cancer

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