Knockdown of CEACAM19 suppresses human gastric cancer through inhibition of PI3K/Akt and NF-κB

Zhao, Hongying; Xu, Jianjun; Wang, Yu; Jiang, Rongke; Li, Xue; Zhang, Lili; Che, Yingqi

doi:10.1016/j.suronc.2018.05.003

Cited by 17 publications

(13 citation statements)

References 31 publications

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“…What work has been done is predominantly focused upon oncology. However, it was observed in oncogenic investigations that CEACAM19 does interact with the AKT/PI3K pathway [13], a pathway known to play a regulatory role in tau phosphorylation. While these studies certainly do not prove a connection between CLPTM1 or CEACAM19 and AD, they do suggest a plausible biological connection that warrants further investigation.…”

Section: Apoc1 -Ceacam19 -Clptm1 Chr19mentioning

confidence: 99%

Multi-Tissue Neocortical Transcriptome-Wide Association Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer’s Disease

Gockley

Montgomery

Poehlman

et al. 2020

Preprint

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AbstractBackgroundAlzheimer’s disease (AD), an incurable neurodegenerative disease, currently affecting 1.75% of the United States population, with projected growth to 3.46% by 2050. Identifying common genetic variants driving differences in transcript expression that confer AD-risk is necessary to elucidate AD mechanism and develop therapeutic interventions. We modify the FUSION Transcriptome Wide Association Study (TWAS) pipeline to ingest expression from multiple neocortical regions, provide a set of 6780 gene weights which are abstracatable across the neocortex, and leverage these to find 8 genes from six loci with associated AD risk validated through summary mendelian randomization (SMR) utilizing IGAP summary statistics.MethodA combined dataset of 2003 genotypes clustered to Central European (CEU) ancestry was used to construct a training set of 790 genotypes paired to 888 RNASeq profiles across 6 Neo-cortical tissues (TCX=248, FP=50, IFG=41, STG=34, PHG=34, DLPFC=461). Following within-tissue normalization and covariate adjustment, predictive weights to impute expression components based on a gene’s surrounding cis-variants were trained. The FUSION pipeline was modified to support input of pre-scaled expression values and provide support for cross validation with a repeated measure design arising from the presence of multiple transcriptome samples from the same individual across different tissues.ResultsCis-variant architecture alone was informative to train weights and impute expression for 6780 (49.67%) autosomal genes, the majority of which significantly correlated with gene expression; FDR < 5%: N=6775 (99.92%), Bonferroni: N=6716 (99.06%). Validation of weights in 515 matched genotype to RNASeq profiles from the CommonMind Consortium (CMC) was (72.14%) in DLPFC profiles. Association of imputed expression components from all 2003 genotype profiles yielded 8 genes significantly associated with AD (FDR < 0.05); APOC1, EED, CD2AP, CEACAM19, CLPTM1, MTCH2, TREM2, KNOP1.ConclusionWe provide evidence of cis-genetic variation conferring AD risk through 8 genes across six distinct genomic loci. Moreover, we provide expression weights for 6780 genes as a valuable resource to the community, which can be abstracted across the neocortex and a wide range of neuronal phenotypes.

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Section: Apoc1 -Ceacam19 -Clptm1 Chr19mentioning

confidence: 99%

Multi-Tissue Neocortical Transcriptome-Wide Association Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer’s Disease

Gockley

Montgomery

Poehlman

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…NF-κB could upregulate levels of various genes that play a role in cell proliferation, migration and apoptosis [29,30] . NF-κB inactivation may also lead to mitochondriapathway-induced apoptosis in colon cancer cells by the way of inhibiting NF-κB/p65 phosphorylation [31,32] , block p65 phosphorylation at Ser536 and IκBα phosphorylation at Ser32, and therefore suppress NF-κB nuclear translocation in gastric cancer cells [33,34] . In addition, activation of ERK1/2 could either induce cell proliferation or apoptosis [35][36][37] .…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Microtubule Associated Serine/threonine Kinase Like Expression Inhibits Gastric Cancer Cell Growth and Induces Apoptosis by Activation of ERK1/2 and Inactivation of NF-κB Signaling

Xie

et al. 2021

CURR MED SCI

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SummaryMicrotubule-associated serine/threonine kinase (MASTL) functions to regulate chromosome condensation and mitotic progression. Therefore, aberrant MASTL expression is commonly implicated in various human cancers. This study analyzed MASTL expression in gastric cancer vs. adjacent normal tissue for elucidating the association with clinicopathological data from patients. This work was then extended to investigate the effects of MASTL knockdown on tumor cells in vitro. The level of MASTL expression in gastric cancer tissue was assessed from the UALCAN, GEPIA, and Oncomine online databases. Lentivirus carrying MASTL or negative control shRNA was infected into gastric cancer cells. RT-qPCR, Western blotting, cell viability, cell counting, flow cytometric apoptosis and cell cycle, and colony formation assays were performed. MASTL was upregulated in gastric cancer tissue compared to the adjacent normal tissue, and the MASTL expression was associated with advanced tumor stage, Helicobacter pylori infection and histological subtypes. On the other hand, knockdown of MASTL expression significantly reduced tumor cell viability and proliferation, and arrested cell cycle at G2/M stage but promoted tumor cells to undergo apoptosis. At protein level, knockdown of MASTL expression enhanced levels of cleaved PARP1, cleaved caspase-3, Bax and p-ERK1/2 expression, but downregulated expression levels of BCL-2 and p-NF-κB-p65 protein in AGS and MGC-803 cells. MASTL overexpression in gastric cancer tissue may be associated with gastric cancer development and progression, whereas knockdown of MASTL expression reduces tumor cell proliferation and induces apoptosis. Further study will evaluate MASTL as a potential target of gastric cancer therapeutic strategy.

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“…MIR3609 (microRNA 3609) had been proven to improve the immune response in breast cancer by blocking the programmed death-ligand 1 immune checkpoint ( 60 ). PLEKHA4 (pleckstrin homology domain containing A4) might be involved in the progression of a tumor through the Wnt pathway ( 61 ). CEACAM19 (CEA cell adhesion molecule 19), DIO3OS (DIO3 opposite strand upstream RNA), and PCAT6 (prostate cancer associated transcript 6) were verified as associated with the prognosis of different cancers, including gastric cancer, breast cancer, liver cancer, and lung cancer ( 62 – 64 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx

Shen

Zhou

et al. 2020

Front. Med.

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Hepatocellular carcinoma (HCC) is a commonly diagnosed cancer with high mortality rates. The immune response plays an important role in the progression of HCC. Immunotherapies are becoming an increasingly promising tool for treating cancers. Advancements in scRNA-seq (single-cell RNA sequencing) have allowed us to identify new subsets in the immune microenvironment of HCC. Yet, distribution of these new cell types and their potential prognostic value in bulk samples from large cohorts remained unclear. This study aimed to investigate the tumor-infiltration and prognostic value of new cell subsets identified by a previous scRNA-seq study in a TCGA HCC cohort using CIBERSORTx, a machine learning method to estimate cell proportion and infer cell-type-specific gene expression profiles. We observed different distributions of tumor-infiltrating lymphocytes between tumor and normal cells. Among these, the CD4-GZMA cell subset showed association with prognosis (log-rank test, p < 0.05). We further analyzed CD4-GZMA cell specific gene expression with CIBERSORTx, and found 19 prognostic genes (univariable cox regression, p < 0.05). Finally, we applied Least absolute shrinkage and selection operator (LASSO) Cox regression to construct an immune risk score model and performed a prognostic assessment of our model in TCGA and ICGC cohorts. Taken together, the immune landscape in HCC bulk samples may be more complex than assumed, with heterogeneity and different tumor-infiltration relative to scRNA-seq results. Additionally, CD4-GZMA cells and their characteristics may yield therapeutic benefits in the immune treatment of HCC.

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Knockdown of CEACAM19 suppresses human gastric cancer through inhibition of PI3K/Akt and NF-κB

Cited by 17 publications

References 31 publications

Multi-Tissue Neocortical Transcriptome-Wide Association Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer’s Disease

Multi-Tissue Neocortical Transcriptome-Wide Association Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer’s Disease

Knockdown of Microtubule Associated Serine/threonine Kinase Like Expression Inhibits Gastric Cancer Cell Growth and Induces Apoptosis by Activation of ERK1/2 and Inactivation of NF-κB Signaling

Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx

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