NLRC5 promotes cell proliferation via regulating the AKT/VEGF-A signaling pathway in hepatocellular carcinoma

He, Yinghua; Li, Mingfang; Zhang, Xing-yan; Meng, Xiao‐Ming; Huang, Cheng; Li, Jun

doi:10.1016/j.tox.2016.06.012

Cited by 30 publications

(34 citation statements)

References 46 publications

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“…43 Recently, the oncogenic role of NLRC5 in human tumours immensely attracts people's attention. 44,45 In our research, the expression levels of NLRC5 were found that significantly elevated in glioma tissues and cell lines. In addition, NLRC5 knockdown remarkably restrained the biological behaviours of glioma cells, which demonstrating that NLRC5 acts as a carcinogen in glioma cells.…”

Section: Discussionmentioning

confidence: 53%

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Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR‐499a‐5p/LMX1A/NLRC5 pathway

Zong

Song

Xue

et al. 2019

J Cellular Molecular Medi

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Dysregulation of long non‐coding RNAs (lncRNAs) confirm that it plays a crucial role in tumourigenesis and malignant progression of glioma. The present study demonstrated that LncRNA secretory carrier membrane protein 1 (SCAMP1) was up‐regulated and functioned as an oncogene in glioma cells. In addition, miR‐499a‐5p was down‐regulated meanwhile exerted tumour‐suppressive function in glioma cells. Subsequently, inhibition of SCAMP1 significantly restrained the cell proliferation, migration and invasion, as well as promoted apoptosis by acting as a molecular sponge of miR‐499a‐5p. Transcription factor LIM homeobox transcription factor 1, alpha (LMX1A) was overexpressed in glioma tissues and cells. Moreover, miR‐499a‐5p targeted LMX1A 3′‐UTR in a sequence‐specific manner. Hence, down‐regulation of SCAMP1 remarkably reduced the expression level of LMX1A, indicating that LMX1A participated in miR‐499a‐5p‐induced tumour‐suppressive effects on glioma cells. Furthermore, knockdown of LMX1A decreased NLR family, CARD domain containing 5 (NLRC5) mRNA and protein expression levels through directly binding to the NLRC5 promoter region. Down‐regulation of NLRC5 obviously inhibited malignant biological behaviours of glioma cells through attenuating the activity of Wnt/β‐catenin signalling pathway. In conclusion, our study clarifies that SCAMP1/miR‐499a‐5p/LMX1A/NLRC5 axis plays a critical role in modulating malignant progression of glioma cells, which provide a novel therapeutic strategy for glioma treatment.

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Section: Discussionmentioning

confidence: 53%

“…NLRC5 belongs to NLR family and plays a physiologically important role in the maintenance of immune homoeostasis . Recently, the oncogenic role of NLRC5 in human tumours immensely attracts people's attention . In our research, the expression levels of NLRC5 were found that significantly elevated in glioma tissues and cell lines.…”

Section: Discussionmentioning

confidence: 56%

Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR‐499a‐5p/LMX1A/NLRC5 pathway

Zong

Song

Xue

et al. 2019

J Cellular Molecular Medi

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“…Knockdown of NLRC5 in HepG2, SMMC-7721, and BEL-7402 cells resulted in somewhat lower cell proliferation rates and silencing of NLRC5 lead to G1 cell cycle arrest ( 42 ). Another study confirmed a correlation of NLRC5 expression and cell proliferation in HCC and suggested that NLRC5 modulates cell proliferation and the expression of VEGF-A in an AKT-dependent manner ( 45 ). There are also data available that link NLRC5 expression to cell migration and invasion, the most important features of malignant cell behavior.…”

Section: Malignant Transformation and Cell Cyclementioning

confidence: 77%

NLRC5 Functions beyond MHC I Regulation—What Do We Know So Far?

et al. 2017

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NLRC5 is a member of the NLR family that acts as a transcriptional activator of MHC class I genes. In line with the function of several related NLR proteins in innate immune responses, there is, however, also ample evidence that NLRC5 contributes to innate and adaptive immune responses beyond the regulation of MHC class I genes. In human and murine cells, for example, NLRC5 was proposed to contribute to inflammatory and type I interferon responses. The role of NLRC5 in these and other cellular processes is hitherto still not well understood and blurred by discrepancies in the reported data. Here, we provide a detailed and critical discussion of the available experimental data on the emerging biological functions of NLRC5 in innate immune responses in men and mice. Better awareness of the multiple roles of NLRC5 will help to define its overall contribution to immune responses and cancer.

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“…p-AKT was distinctly suppressed in HSC-T6 cells exposed to LY294002 (Fig. 8d ), an inhibitor of PI3K/AKT 22 . Interestingly, expression of C-myc and CyclinD1 was restored following blockade of PI3K/AKT in HSC-T6 cells with enforced SUN2 expression.…”

Section: Resultsmentioning

confidence: 95%

Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis

Chen

et al. 2018

Cell Death Dis

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Hepatic myofibroblasts, activated hepatic stellate cells (HSCs), are the main cell type of extracellular matrix (ECM) deposition during hepatic fibrosis. Aberrant DNA methylation-regulated HSCs activation in liver fibrogenesis has been reported, but the functional roles and mechanisms of DNA methylation in hepatic fibrosis remain to be elucidated. In the present study, reduced representation bisulfite sequencing (RRBS) analysis of primary HSCs revealed hypermethylation patterns in hepatic fibrosis. Interestingly, we found SAD1/UNC84 domain protein-2 (SUN2) gene hypermethylation at CpG sites during liver fibrogenesis in mice with CCl4-induced hepatic fibrosis, which was accompanied by low expression of SUN2. In vivo overexpression of SUN2 following adeno-associated virus-9 (AAV9) administration inhibited CCl4-induced liver injury and reduced fibrogenesis marker expression. Consistently, in vitro experiments showed that enforced expression of SUN2 suppressed HSCs activation and exerted anti-fibrogenesis effects in TGF-β1-activated HSC-T6 cells. In addition, the signaling mechanisms related to SUN2 expression were investigated in vivo and in vitro. Methyltransferase-3b (DNMT3b) is the principal regulator of SUN2 expression. Mechanistically, inhibition of protein kinase B (AKT) phosphorylation may be a crucial pathway for SUN2-mediated HSCs activation. In conclusion, these findings provide substantial new insights into SUN2 in hepatic fibrosis.

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NLRC5 promotes cell proliferation via regulating the AKT/VEGF-A signaling pathway in hepatocellular carcinoma

Cited by 30 publications

References 46 publications

Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR‐499a‐5p/LMX1A/NLRC5 pathway

Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR‐499a‐5p/LMX1A/NLRC5 pathway

NLRC5 Functions beyond MHC I Regulation—What Do We Know So Far?

Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis

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