Up-Regulation of RACGAP1 Promotes Progressions of Hepatocellular Carcinoma Regulated by GABPA via PI3K/AKT Pathway

Gu, Yang; Chen, Baiyang; Guo, Deliang; Pan, Leyu; Luo, Xiaofeng; Tang, Jie; Yang, Weihua; Zhang, Yuxian; Zhang, Liangqiang; Huang, Jingwen; Duan, Rui; Wang, Zhigang

doi:10.1155/2022/3034150

Cited by 11 publications

(7 citation statements)

References 38 publications

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“…As ECT2 showed important roles in affecting the clinical outcome, tumor stage, grade, and immune cell infiltration, we investigated the molecular interactions of ECT2, where two proteins, namely RACGAP1 and KIF23, were common ones in the two lists of “ECT2-interacting” and “ECT2-correlated” proteins. It was not a surprise that both of these proteins correlated with the progression of several types of human cancers [ 94 , 95 , 96 , 97 ]. Consequently, this interaction pathway could be a potential target for novel antitumor medications.…”

Section: Discussionmentioning

confidence: 99%

Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy

Soltan

Eldeen

Sajer

et al. 2023

Biology

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Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers. The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival. Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival. Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.

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Section: Discussionmentioning

confidence: 99%

Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy

Soltan

Eldeen

Sajer

et al. 2023

Biology

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“…Similarly, high nuclear RACGAP1 expression is associated with poor survival in patients with colorectal cancer ( 51 ). In HCC, RACGAP1 overexpression promotes disease progression and has been reported to be significantly associated with worse overall survival ( 16 , 17 ). In the present study, knockdown of RACGAP1 significantly suppressed cell proliferation and induced apoptosis, whilst overexpression of RACGAP1 significantly promoted cell proliferation and suppressed apoptosis in Huh-7 and Hep3B cells under hypoxic conditions.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal expression of RACGAP1 has been implicated in the pathogenesis and progression of numerous malignant tumors ( 14 , 15 ). For example, recent studies have reported that upregulation of RACGAP1 can be an indicator of a worse overall survival rate in patients with HCC ( 16 ). The activation of RACGAP1 and demethylation of its promoter region, specifically at the H3K4me2 site, have been reported to promote early recurrence, metastasis and microvascular invasion in HCC ( 17 , 18 ).…”

Section: Introductionmentioning

confidence: 99%

HIF‑1α and RACGAP1 promote the progression of hepatocellular carcinoma in a mutually regulatory way

Wu,

Xu,

et al. 2023

Mol Med Rep

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Hypoxia, a condition characterized by low oxygen levels, serves an important role in the progression of hepatocellular carcinoma (HCC). However, the precise molecular mechanisms underlying hypoxia-induced HCC progression are yet to be fully elucidated. The present study assessed the involvement of two key factors, hypoxia-inducible factor-1α (HIF-1α) and Rac GTPase activating protein 1 (RACGAP1), in HCC development under hypoxic conditions. HIF-1α and RACGAP1 genes were overexpressed and knocked down in Hep3B and Huh7 cells using lentiviral transduction and the levels of HIF-1α and RACGAP1 in the cells were assessed using quantitative PCR, western blotting and immunofluorescence. Co-immunoprecipitation experiments were performed to evaluate the interaction between HIF-1α and RACGAP1. Subsequently, the proliferation, apoptosis, migration and invasion of Hep3B and Huh7 cells were assessed using the Cell Counting Kit-8 assay, flow cytometry, Transwell assay and migration experiments. The expression levels of HIF-1α and RACGAP1 in normal and HCC tumor samples were analyzed utilizing the Gene Expression Profiling Interactive Analysis database. Furthermore, correlations between HIF-1α/RACGAP1 gene expression levels and patient survival outcomes were evaluated using the Kaplan-Meier plotter. Knockdown of HIF-1α resulted in a significant decrease in RACGAP1 expression, whilst overexpression of HIF-1α resulted in a significant increase in RACGAP1 expression. Moreover, overexpression and knockdown of RACGAP1 had the same effect on HIF-1α expression. Additionally, it was demonstrated that HIF-1α and RACGAP1 interacted directly within a complex. Overexpression of HIF-1α or RACGAP1 significantly increased proliferation, invasion and migration, and significantly decreased the proportion of apoptotic Hep3B and Huh7 cells. Conversely, knockdown of HIF-1α or RACGAP1 significantly decreased proliferation, invasion and migration, and significantly increased the proportion of apoptotic Hep3B and Huh7 cells. In addition, the combined knockdown or overexpression of HIF-1α and RACGAP1 had a more pronounced effect on HCC cell migration compared with knockdown of HIF-1α alone. Furthermore, there was a significant positive correlation between the expression levels of HIF-1α and RACGAP1 in HCC tissues and patients with HCC and upregulation of both HIF-1α and RACGAP1 demonstrated a lower overall survival probability. In conclusion, HIF-1α and RACGAP1 may synergistically contribute to the development of HCC, highlighting their potential as valuable targets for HCC therapy.

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“…To further confirm and evaluate potential therapeutic values from the novel identified up-regulated DEGs with the impacts of decreased survival in the current study, we chose to validate genes that were the top ten up-regulated DEGs with decreased survival and not shown to be associated with tumorigenesis. Among them, studies have proved that CCNB1, RACGAP1 and NUSAP1 promote the progression of multiple cancers (Aljohani et al 2022;Gu et al 2022;Guo et al 2020), and NCAPG and CCNB2 have been found to be associated with a poor prognosis of ES (Kakar et al 2022;Zhao et al 2022), while ASPM, CENPF, CKS2, and DTL have not been studied in ES to the best of our knowledge. Interestingly, these four genes were also found in the GO analysis and GSEA results (Fig.…”

Section: In Vitro Verification Of Four Up-regulated Degs With Decreas...mentioning

confidence: 97%

Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma

Cao

Sun

Fan

et al. 2023

J Cancer Res Clin Oncol

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Purpose To explore transcriptome and immunological features of patients with Ewing sarcoma (ES) using all publicly available microarray data. Methods Data of 479 ES tissues were integrated and normalized. Gene expression, immune infiltration, and cancer-specific pathways were analyzed. Genes of interest were knocked down, followed by cell proliferation and colony formation assays. Results Consistent with the previous reports of differential expressed genes (DEGs) in ES, our analysis identified CCND1, HMCN1, and NKX2-2 were among the most highly expressed, while TWNC1, MYBPC1, and CKM were among the lowest expressed genes. GO, KEGG, and GSEA enrichment analysis identified that the DEGs related to bone and muscle functioning, those that contributed to crucial cellular, and metabolism pathways such as actin binding, apoptosis, TCA cycle, and cell cycle were also significantly enriched. Immune infiltration analysis discovered that many T cell subsets including CD4T, CD8 T, and Gamma delta T cells were highly infiltrated, while monocytes and B cells were less infiltrated in tumors. A total of 138 genes were both significantly up-regulated in tumors and associated with decreased survival, while 38 significantly down-regulated genes were associated with increased survival, many of which were previously reported as oncogenes and tumor suppressors in ES and other cancers. Silencing of four newly identified top ranked up-regulated genes with decreased survivals in ES inhibited proliferation and colony formation of ES cells. Conclusion This study may provide a clear representative transcriptome profile of ES, providing diagnostic biomarkers, pathways, and immune infiltrative characteristics targets for ES.

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Up-Regulation of RACGAP1 Promotes Progressions of Hepatocellular Carcinoma Regulated by GABPA via PI3K/AKT Pathway

Cited by 11 publications

References 38 publications

Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy

Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy

HIF‑1α and RACGAP1 promote the progression of hepatocellular carcinoma in a mutually regulatory way

Integrative analyses of bulk microarray data to discover genes, pathways, and immune infiltration characteristics associated with targeting of Ewing sarcoma

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