New Approach about the Signaling Crosstalk between IQGAPs/ NF- κB/IL-8 and PDCD5/p53/TRAIL Pathways that Modulate Malignant Transformation in Hepatocellular Carcinoma

Zoheir, Khairy M.A.; Abdelhafez, Mohamed A.; Darwish, Ahmed M.; Mahrous, Karima F.

doi:10.31557/apjcp.2022.23.1.271

Cited by 8 publications

(10 citation statements)

References 33 publications

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“…were independent risk factors of HCC [42]. IQGAP1 is known to be overexpressed in HCC [43]. Zhao et al and Lai et al reported that CDC20 as tumor promoters in HCC [44,45].…”

Section: Discussionmentioning

confidence: 99%

NamiRNA-mediated high expression of KNSTRN correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

Jin

Zhang

Fan

et al. 2023

Preprint

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Background Kinetochore localized astrin/SPAG5 binding protein (KNSTRN) plays an important molecular in cell division. Mutations of KNSTRN can interfere with chromatid cohesion, increase aneuploidy in tumors, enhancing tumorigenesis. Additionally, the concept of nuclear activating miRNA (NamiRNA) has been proposed with encouraging results. However, the role of KNSTRN in Hepatocellular Carcinoma (HCC) remains not fully determined, and the underlying molecular mechanisms of this differential regulation of KNSTRN by a NamiRNA are also unclear in HCC. Methods Based on Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, we first investigated the potential oncogenic functions of KNSTRN and a potential NamiRNA Using R and various computational tools in HCC. Results Detailed results revealed that elevated expression of KNSTRN was considerably associated with bad overall survival (HR = 1.48, 95%CI 1.05–2.09, P = 0.027) and progress free interval (HR = 1.41, 95%CI 1.05–1.89, P = 0.021) in HCC. GO/KEGG functional enrichment analysis showed that KNSTRN is closely related to organelle fission, chromosomal region, tubulin binding, and cell cycle signaling pathway. TIMER databases analysis showed the correlations between KNSTRN expression and tumor-infiltrating immune cells, biomarkers of immune cells and immune checkpoint expression. Moreover, KNSTRN level was significantly positively associated with immunosuppressive cell in tumor microenvironment (TME), including regulatory T cells (Tregs), myeloid derived suppressor cells (MDSCs), and cancer-associated fibrocytes (CAFs). Further, hsa-miR-107 is determined as a potential Nuclear activating miRNA (NamiRNA) by correlation analysis. High expression of hsa-miR-107 is negatively correlated with disease specific survival (HR = 0.62, 95%CI 0.4–0.98, P = 0.04) in patients with HCC by targeting the oncogene, KNSTRN. Finally, a possible NamiRNA-enhancer network of hsa-miR-107 activates the KNSTRN expression in LIHC were constructed. Conclusion The hsa-miR-107-mediated upregulation of KNSTRN correlated with poor prognosis and tumor immune infiltration in HCC.

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“…were independent risk factors of HCC [42]. IQGAP1 is known to be overexpressed in HCC [43]. Zhao et al and Lai et al reported that CDC20 as tumor promoters in HCC [44,45].…”

Section: Discussionmentioning

confidence: 99%

NamiRNA-mediated high expression of KNSTRN correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

Jin

Zhang

Fan

et al. 2023

Preprint

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“…IQGAPs have attracted increasing interest in cancer research because of their fundamental contribution to cytoskeletal remodeling and signal transduction. Numerous studies have shown an association between IQGAPs and HCC initiation, metastasis, and recurrence, as well as poor prognosis in patients with HCC ( 10 , 16 – 24 , 29 , 81 , 90 – 98 ) (details in Table 1 ).…”

Section: The Relationship Between Iqgaps and Liver Diseasesmentioning

confidence: 99%

“…However, the mRNA expressions of members of Ras gene family significantly decreased after IQGAP1 silencing, which was accompanied by reduced proliferation and invasion ability of HCC cells ( 97 ). In addition, ERK and AKT may be involved in IQGAP1-induced elevation of NF-κB, promoting tumorigenesis, metastasis, and resistance to apoptosis ( 10 , 123 , 124 ). These results suggest that IQGAP1 may activate the MAPK/ERK signaling pathway by upregulating Ras gene family expression to promote hepatocarcinogenesis and progression.…”

Section: Action Mechanism Of Iqgaps In Hccmentioning

confidence: 99%

“…These homologs comprise multiple domains involved in regulating a broad spectrum of biological processes such as cytoskeleton remodeling, cytokinesis, protein trafficking, cell adhesion, proliferation, migration, and tumorigenesis ( 1 – 6 ). Aberrant IQGAP expression has been extensively reported in a range of malignancies, including liver, gastric, lung, breast, and colon cancers, and is highly related to poor clinical characteristics and prognosis ( 7 – 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

et al. 2022

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IQ motif-containing GTPase-activating proteins (IQGAPs) are a class of scaffolding proteins, including IQGAP1, IQGAP2, and IQGAP3, which govern multiple cellular activities by facilitating cytoskeletal remodeling and cellular signal transduction. The role of IQGAPs in cancer initiation and progression has received increasing attention in recent years, especially in hepatocellular carcinoma (HCC), where the aberrant expression of IQGAPs is closely related to patient prognosis. IQGAP1 and 3 are upregulated and are considered oncogenes in HCC, while IQGAP2 is downregulated and functions as a tumor suppressor. This review details the three IQGAP isoforms and their respective structures. The expression and role of each protein in different liver diseases and mainly in HCC, as well as the underlying mechanisms, are also presented. This review also provides a reference for further studies on IQGAPs in HCC.

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“…IQGAPs are considered to play a comprehensive and distinct role in HCC and therefore warrant more research to explore the concrete mechanisms of IQGAPs in HCC [10]. IQGAP1 has been shown to be upregulated in HCC as well as being involved in the oncogenic process [11][12][13][14][15]. Xu et al reported that IQGAP1 could interact with CDC42 to stimulate cell division, thus promoting the proliferation of HuH-7 cells [11].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of the expression and prognosis for IQ motif-containing GTPase-activating proteins in hepatocellular carcinoma

Dai

Song

et al. 2022

BMC Cancer

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Background IQ motif-containing GTPase-activating proteins (IQGAPs) are a group of scaffold proteins which have been identified to be involved in tumor initiation and progression in diverse types of cancer. Clinical studies and experimental evidence suggest that IQGAPs play an essential role in hepatocellular carcinoma (HCC) progression and alterations in their expression are closely related to patient prognosis. However, the different expression patterns and prognostic values of all three IQGAP isoforms in HCC have not yet been analyzed simultaneously. Methods We analyzed the transcriptional and survival data of IQGAPs in HCC patients using Oncomine, UALCAN, Kaplan–Meier Plotter, cBioPortal, and GeneMANIA. We further examined tumor and adjacent normal tissues from 250 HCC patients using immunohistochemistry to assess the relationship between IQGAPs expression and clinicopathological features and validate the prognostic value of IQGAPs. In addition, we analyzed transcriptional changes of IQGAPs with regards to survival data in HCC patients from the TCGA-LIHC (liver hepatocellular carcinoma) cohort to validate our results. Results We found that the expression levels of IQGAP1 and 3 were significantly elevated in HCC tissues than in normal liver tissues, whereas the expression level of IQGAP2 was decreased in the former than in the latter. The clinical data showed that positive IQGAP1 expression was associated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, poor relapse-free survival (RFS), and overall survival (OS), and positive IQGAP3 expression was associated with poorer tumor differentiation, RFS, and OS. Conversely, positive IQGAP2 expression predicted less tumor numbers and microvascular invasion, as well as higher RFS and OS in these patients. Conclusions IQGAPs may serve as new prognostic biomarkers and potential targets for precision therapy in HCC.

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New Approach about the Signaling Crosstalk between IQGAPs/ NF- κB/IL-8 and PDCD5/p53/TRAIL Pathways that Modulate Malignant Transformation in Hepatocellular Carcinoma

Abstract: and the third most common reason of cancer-related mortality (Sayiner et al., 2019). Due to the fact that most HCC patients have acquired cirrhosis, chemotherapy regimen or major resections are not efficiently tolerated (Wang et al.

Cited by 8 publications

References 33 publications

NamiRNA-mediated high expression of KNSTRN correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

NamiRNA-mediated high expression of KNSTRN correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

Comprehensive analysis of the expression and prognosis for IQ motif-containing GTPase-activating proteins in hepatocellular carcinoma

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