PLXNC1 Enhances Carcinogenesis Through Transcriptional Activation of IL6ST in Gastric Cancer

Chen, Jie; Liu, Haining; Chen, Jinggui; Sun, Bo; Wu, Jianghong; Du, Chunyan

doi:10.3389/fonc.2020.00033

Cited by 13 publications

(11 citation statements)

References 21 publications

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“…Further, as NFkB is suggested to drive TAMs towards a more anti-inflammatory environment, it is plausible that this subpopulation plays a role in the observed peripheral cells' evolution towards an anti-inflammatory environment. Furthermore the enrichment of other transcription factors from the same cluster (BATF, PLXNC1, MTF1) as NFkB have been shown to upregulate in other cancers [72][73][74] suggesting NFkB to exert and a pro-tumor effect.…”

Section: Discussionmentioning

confidence: 99%

Distinct regional ontogeny and activation of tumor associated macrophages in human glioblastoma

Landry

Balas

Alli

et al. 2020

Sci Rep

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Tumor-associated macrophages (TAMs) constitute up to 50% of tumor bulk in glioblastoma (GBM) and play an important role in tumor maintenance and progression. The recently discovered differences between invading tumour periphery and hypoxic tumor core implies that macrophage biology is also distinct by location. This may provide further insight into the observed treatment resistance to immune modulation. We hypothesize that macrophage activation occurs through processes that are distinct in tumor periphery versus core. We therefore investigated regional differences in TAM recruitment and evolution in GBM by combining open source single cell and bulk gene expression data. We used single cell gene expression data from 4 glioblastomas (total of 3589 cells) and 122 total bulk samples obtained from 10 different patients. Cell identity, ontogeny (bone-marrow derived macrophages-BMDM vs microglia), and macrophage activation state were inferred using verified gene expression signatures. We captured the spectrum of immune states using cell trajectory analysis with pseudotime ordering. In keeping with previous studies, TAMs carrying BMDM identity were more abundant in tumor bulk while microglia-derived TAMs dominated the tumor periphery across all macrophage activation states including pre-activation. We note that core TAMs evolve towards a pro-inflammatory state and identify a subpopulation of cells based on a gene program exhibiting strong, opposing correlation with Programmed cell Death-1 (PD-1) signaling, which may correlate to their response to PD-1 inhibition. By contrast, peripheral TAMs evolve towards anti-inflammatory phenotype and contains a population of cells strongly associated with NFkB signaling. Our preliminary analysis suggests important regional differences in TAMs with regard to recruitment and evolution. We identify regionally distinct and potentially actionable cell subpopulations and advocate the need for a multi-targeted approach to GBM therapeutics.

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Section: Discussionmentioning

confidence: 99%

Distinct regional ontogeny and activation of tumor associated macrophages in human glioblastoma

Landry

Balas

Alli

et al. 2020

Sci Rep

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“…In addition, it is involved in local tissue remodeling and immune cell infiltration ( Feigerlovã and Battaglia-Hsu, 2017 ). The IL-6/STAT3 signaling pathway has been investigated in gastric cancer research, and activation of IL6ST enhances carcinogenesis ( Chen et al, 2020 ). Although it has been previously reported that IL-6 stimulates STAT3 phosphorylation in acute kidney injury, the mechanism of IL-6 in the STAT3/NF-kB signaling pathway remains to be investigated ( Ranganathan et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

lncRNA MALAT1 Promotes Renal Fibrosis in Diabetic Nephropathy by Targeting the miR-2355-3p/IL6ST Axis

Huang

Zhang

2021

Front. Pharmacol.

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Long noncoding RNA (lncRNAs) metastasis–associated lung adenocarcinoma transcript 1 (MALAT1) has been reported in diabetic nephropathy (DN) about its effect on podocyte function and cell heat shock induced by hyperglycemia. However, the biological mechanism of MALAT1 regulating DN fibrosis needs further study. In this study, SD rats were administrated with streptozotocin (STZ) to establish a diabetes model. In vitro, human renal tubular epithelial cells (HK-2 and 293T) were treated with high glucose (HG). Here, we found that MALAT1 was upregulated in renal tissues of diabetic rats and HG-treated cells, and HG treatment promoted cell proliferation and invasion. MALAT1 overexpression aggravated protein levels of collagen I (col I), collagen IV (col IV), fibronectin (FN), and laminin (LN) in HK-2 cells, while MALAT1 knockdown exerted the opposite effect. Moreover, the luciferase reporter gene and pull-down assays demonstrated that MALAT1 interacted with miR-2355-3p. The miR-2355-3p level was downregulated in diabetic rats and HG-treated cells, and MALAT1 overexpression inhibited the miR-2355-3p level. Bioinformatics prediction and luciferase reporter gene assay revealed that interleukin 6 signal transducer (IL6ST) was a target of miR-2355-3p. In addition, miR-2355-3p overexpression attenuated fibrosis-related gene levels in HG-treated cells by inhibiting IL6ST expression and inactivating the recombinant signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Knockdown of miR-2355-3p reversed the inhibitory effect of MALAT1 knockdown on IL6ST, col I, col IV, FN, and LN protein levels in HG-induced cells. Overexpression of MALAT1 aggravated cell damage in HG-induced cells via the miR-2355-3p/IL6ST/STAT3 signaling pathway. Finally, enhanced renal fibrosis and kidney tissue damage were observed in diabetic rats. In conclusion, MALAT1 overexpression may enhance renal fibrosis in diabetic rats and cell damage in HG-induced HK-2 cells via the miR-2355-3p/IL6ST axis, which provides a new perspective of DN treatment.

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“…The expression levels of certain genes altered following treatment of JQ1 and SAHA, indicating that these drugs might inhibit tumor growth by regulating the expression of some key genes. PLXNC1 is reported as an oncogene in liver carcinoma (Odabas et al, 2018) and gastric cancer (Chen et al, 2020) and also played a part in TC progression. MiR-4500 repressed PTC development by decreasing PLXNC1 expression (Li et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Histone H3K27 Acetylation Profiling Identified Genes Correlated With Prognosis in Papillary Thyroid Carcinoma

Zhang

Xiong

Liu

et al. 2021

Front. Cell Dev. Biol.

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Thyroid carcinoma (TC) is the most common endocrine malignancy, and papillary TC (PTC) is the most frequent subtype of TC, accounting for 85–90% of all the cases. Aberrant histone acetylation contributes to carcinogenesis by inducing the dysregulation of certain cancer-related genes. However, the histone acetylation landscape in PTC remains elusive. Here, we interrogated the epigenomes of PTC and benign thyroid nodule (BTN) tissues by applying H3K27ac chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) along with RNA-sequencing. By comparing the epigenomic features between PTC and BTN, we detected changes in H3K27ac levels at active regulatory regions, identified PTC-specific super-enhancer-associated genes involving immune-response and cancer-related pathways, and uncovered several genes that associated with disease-free survival of PTC. In summary, our data provided a genome-wide landscape of histone modification in PTC and demonstrated the role of enhancers in transcriptional regulations associated with prognosis of PTC.

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PLXNC1 Enhances Carcinogenesis Through Transcriptional Activation of IL6ST in Gastric Cancer

Cited by 13 publications

References 21 publications

Distinct regional ontogeny and activation of tumor associated macrophages in human glioblastoma

Distinct regional ontogeny and activation of tumor associated macrophages in human glioblastoma

lncRNA MALAT1 Promotes Renal Fibrosis in Diabetic Nephropathy by Targeting the miR-2355-3p/IL6ST Axis

Genome-Wide Histone H3K27 Acetylation Profiling Identified Genes Correlated With Prognosis in Papillary Thyroid Carcinoma

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