GNA14’s interaction with RACK1 inhibits hepatocellular carcinoma progression through reducing MAPK/JNK and PI3K/AKT signaling pathway

Xu, Cong; Li, Yiming; Sun, Bo; Zhong, Fang-Jing; Yang, Lian-Yue

doi:10.1093/carcin/bgab098

Cited by 16 publications

(9 citation statements)

References 39 publications

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“…43,44 The PIK3CA gains, together with frequently observed losses of GNA14, and forkhead box O3 (FOXO3) genes suggest dysregulation of the PI3K-AKT pathway in MCL, both at diagnosis, and (even more) at relapse. 45,46 The most frequent newly mutated gene at relapse was a tumor suppressor low-density lipoprotein receptor-related protein 1B (LRP1B, 3 new variants in 2 patients, in total 6 out of 25 patients at relapse, 28%). Inactivation of LRP1B by diverse genetic and epigenetic mechanisms belongs to the most frequent alternations in human cancer overall.…”

Section: Discussionmentioning

confidence: 99%

Sequencing‐based analysis of clonal evolution of 25 mantle cell lymphoma patients at diagnosis and after failure of standard immunochemotherapy

Karolová,

Kazantsev,

Svatoň

et al. 2023

American J Hematol

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Our knowledge of genetic aberrations, that is, variants and copy number variations (CNVs), associated with mantle cell lymphoma (MCL) relapse remains limited. A cohort of 25 patients with MCL at diagnosis and the first relapse after the failure of standard immunochemotherapy was analyzed using whole‐exome sequencing. The most frequent variants at diagnosis and at relapse comprised six genes: TP53, ATM, KMT2D, CCND1, SP140, and LRP1B. The most frequent CNVs at diagnosis and at relapse included TP53 and CDKN2A/B deletions, and PIK3CA amplifications. The mean count of mutations per patient significantly increased at relapse (n = 34) compared to diagnosis (n = 27). The most frequent newly detected variants at relapse, LRP1B gene mutations, correlated with a higher mutational burden. Variant allele frequencies of TP53 variants increased from 0.35 to 0.76 at relapse. The frequency and length of predicted CNVs significantly increased at relapse with CDKN2A/B deletions being the most frequent. Our data suggest, that the resistant MCL clones detected at relapse were already present at diagnosis and were selected by therapy. We observed enrichment of genetic aberrations of DNA damage response pathway (TP53 and CDKN2A/B), and a significant increase in MCL heterogeneity. We identified LRP1B inactivation as a new potential driver of MCL relapse.

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Section: Discussionmentioning

confidence: 99%

Sequencing‐based analysis of clonal evolution of 25 mantle cell lymphoma patients at diagnosis and after failure of standard immunochemotherapy

Karolová,

Kazantsev,

Svatoň

et al. 2023

American J Hematol

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“…And the expression of GNA14 is decreased in tumor tissues and is related to the poor OS of patients with HCC, indicating that it can be a tumor suppressor gene. Recent research has demonstrated this view that GNA14 inhibits HCC progression by interacting with RACK1 and attenuating MAPK/JNK and PI3K/AKT axis [ 44 ]. About EGF, numerous studies have demonstrated its capacity of mediating the malignant biological behavior of HCC is reached through interacting with EGF receptor (EGFR) and activating specific oncogenic signaling pathways, like ERK and PI3K axis [ 45 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Analysis of Platelet-Related Genes in Hepatocellular Carcinoma Reveals a Novel Prognostic Signature and Determines PRKCD as the Potential Molecular Bridge

Zhao

Lü

et al. 2022

Biol Proced Online

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Background Hepatocellular carcinoma (HCC) belongs to a representative lethality gastrointestinal malignancy, and comprehensive management of HCC remains intractable at present on account of its invasive biological feature that is easy to relapse and early metastasis. The intimate connection between platelets and tumor progression has been widely reported, and platelet-related indicators are also used in the clinical practice of carcinoma. This work is designed to investigate the significance of platelet-related genes in the prognostic prediction of patients with HCC and their potential role in the cross-talk between HCC cells and platelets in the tumor microenvironment. Methods By integrating the RNA-seq data and clinicopathological information of HCC patients, we extracted prognosis-associated platelet-related genes based on the univariate cox analysis and further established a relevant prognostic signature via the lasso cox regression analysis, and two independent HCC cohorts were used as external validation. Multiple bioinformatics methods were utilized to explore the underlying functional discrepancy between different risk groups classified by the risk model. And in vitro proliferation, invasion, and migration assays were conducted to investigate the effect of platelet stimulation on HCC cells’ viability and motility, and flow cytometric analysis was exerted to demonstrate the influence of HCC cells on platelet activation. Results A novel platelet-related risk model was developed and patients both in the training and testing cohorts were divided into distinct risk subgroups according to the median risk score. It was observed that the high-risk status was closely associated with poor prognosis and worse clinicopathological parameters. Meanwhile, an obvious discrepancy in the constitution of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. Moreover, in vitro experiments demonstrated that PRKCD could act as a molecular bridge between tumor cells and platelets, which could either participate in regulating tumor malignant phenotype or mediating platelet activation. Conclusions In brief, this work reveals a novel platelet-related risk signature for prognostic evaluation of HCC patients and confirms that PRKCD is a key messenger in HCC cell-platelet interaction and plays a crucial role in mediating platelet-induced tumor progression.

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“…Meanwhile, CYP2C9 is also down-regulated in HCC ( Yu et al, 2015 ). GNA14 is down-expressed and inhabits HCC progression through MAPK / JNK and PI3K / AKT signaling pathways ( Xu et al, 2021 ). In addition, hypermethylation of GNA14 promoter is upregulated in HCC ( Song et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and analysis of DNA methylation-driven signatures for prognostic and immune microenvironments evaluation in hepatocellular carcinoma

Shen

Wen

et al. 2022

Front. Genet.

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Liver cancer is the main reason of cancer deaths globally, with an unfavorable prognosis. DNA methylation is one of the epigenetic modifications and maintains the right adjustment of gene expression and steady gene silencing. We aim to explore the novel signatures for prognosis by using DNA methylation-driven genes. To acquire the DNA methylation-driven genes, we perform the difference analysis from the gene expression data and DNA methylation data in TCGA or GEO databases. And we obtain the 31 DNA methylation-driven genes. Subsequently, consensus clustering analysis was utilized to identify the molecular subtypes based on the 31 DNA methylation-driven genes. So, two molecular subtypes were identified to perform those analyses: Survival, immune cell infiltration, and tumor mutation. Results showed that two subtypes were clustered with distinct prognoses, tumor-infiltrating immune cell and tumor mutation burden. Furthermore, the 31 DNA methylation-driven genes were applied to perform the survival analysis to select the 14 survival-related genes. Immediately, a five methylation-driven genes risk model was built, and the patients were divided into high and low-risk groups. The model was established with TCGA as the training cohort and GSE14520 as the validation cohort. According to the risk model, we perform the systematical analysis, including survival, clinical feature, immune cell infiltration, somatic mutation status, underlying mechanisms, and drug sensitivity. Results showed that the high and low groups possessed statistical significance. In addition, the ROC curve was utilized to measure the accuracy of the risk model. AUCs at 1-year, 3-years, and 5-years were respectively 0.770, 0.698, 0.676 in training cohort and 0.717, 0.649, 0.621 in validation cohort. Nomogram was used to provide a better prediction for patients’ survival. Risk score increase the accuracy of survival prediction in HCC patients. In conclusion, this study developed a novel risk model of five methylation-driven genes based on the comprehensive bioinformatics analysis, which accurately predicts the survival of HCC patients and reflects the immune and mutation features of HCC. This study provides novel insights for immunotherapy of HCC patients and promotes medical progress.

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GNA14’s interaction with RACK1 inhibits hepatocellular carcinoma progression through reducing MAPK/JNK and PI3K/AKT signaling pathway

Cited by 16 publications

References 39 publications

Sequencing‐based analysis of clonal evolution of 25 mantle cell lymphoma patients at diagnosis and after failure of standard immunochemotherapy

Sequencing‐based analysis of clonal evolution of 25 mantle cell lymphoma patients at diagnosis and after failure of standard immunochemotherapy

Genetic Analysis of Platelet-Related Genes in Hepatocellular Carcinoma Reveals a Novel Prognostic Signature and Determines PRKCD as the Potential Molecular Bridge

Identification and analysis of DNA methylation-driven signatures for prognostic and immune microenvironments evaluation in hepatocellular carcinoma

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