DIAPH1 Is Upregulated and Inhibits Cell Apoptosis through ATR/p53/Caspase-3 Signaling Pathway in Laryngeal Squamous Cell Carcinoma

Yang, Jin; Zhou, Liang; Zhang, Yanping; Zheng, Jie; Zhou, Jian; Wei, Zhe-Qiang; Zou, J. J.

doi:10.1155/2019/6716472

Cited by 27 publications

(22 citation statements)

References 29 publications

(35 reference statements)

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“…In addition, a recent study recorded that cytochrome P450 inhibited the activity of the metabolic enzymes CYP2C9 Ã 2 and CYP2C9 Ã 3, which could directly control tumorigenesis by reducing epoxyeicosatrienoic acid production (Hunter et al, 2015;Katiyar et al, 2017). The PI3K-Akt signalling pathway has a vital function in LSCC by suppressing cell death (Chrysovergis et al, 2019;Yang et al, 2019). P53, a tumour suppressor factor, initiates DNA repair, cell cycle arrest and apoptosis and reacts to various kinds of cancer therapies (Cui, Qu & Liu, 2019;Ragos et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of laryngeal squamous cell carcinoma: seeking key candidate genes and pathways

Ma¹,

Hu²,

Dai³

et al. 2021

PeerJ

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Background Laryngeal squamous cell carcinoma (LSCC) is the second most aggressive head and neck squamous cell carcinoma. Although much work has been done to optimize its treatment, patients with LSCC still have poor prognosis. Therefore, figuring out differentially expressed genes (DEGs) contained in the progression of LSCC and employing them as potential therapeutic targets or biomarkers for LSCC is extremely meaningful. Methods Overlapping DEGs were screened from two standalone Gene Expression Omnibus datasets, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. By applying STRING and Cytoscape, a protein–protein network was built, and module analysis was carried out. The hub genes were selected by maximal clique centrality with the CytoHubba plugin of Cytoscape. UALCAN and GEPIA data were examined to validate the gene expression findings. Moreover, the connection of the hub genes with LSCC patient overall survival was studied employing The Cancer Genome Atlas. Then, western blot, qRT-PCR, CCK-8, wound healing and transwell assays were bring to use for further verify the key genes. Results A total of 235 DEGs were recorded, including 83 upregulated and 152 downregulated genes. A total of nine hub genes that displayed a high degree of connectivity were selected. UALCAN and GEPIA databases verified that these genes were highly expressed in LSCC tissues. High expression of the SPP1, SERPINE1 and Matrix metalloproteinases 1 (MMP1) genes was connected to worse prognosis in patients with LSCC, according to the GEPIA online tool. Western blot and qRT-PCR testify SPP1, SERPINE1 and MMP1 were upregulated in LSCC cells. Inhibition of SPP1, SERPINE1 and MMP1 suppressed cell proliferation, invasion and migration. Conclusion The work here identified effective and reliable diagnostic and prognostic molecular biomarkers by unified bioinformatics analysis and experimental verification, indicating novel and necessary therapeutic targets for LSCC.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis of laryngeal squamous cell carcinoma: seeking key candidate genes and pathways

Ma¹,

Hu²,

Dai³

et al. 2021

PeerJ

View full text Add to dashboard Cite

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“…The frameshift mutations that reside on FH1-FH2 domain with active actin bonding property might reduce the actin bonding capability by generating a stop codon in the early phase of the polypeptide of 1263 amino acid residues. [19,25] Although the high levels of DIAPH1 mRNA are a boosting factor for metastasis progression, the advent of resistance against chemotherapy medicine might lead to a negative prognosis.…”

Section: Discussionmentioning

confidence: 99%

Why Cytoskeletal Associated Proteins are Important in Colorectal Cancer Patients: Molecular & Bioinformatic Analysis

Balı¹,

Özkan²

2021

Lokman Hekim Health Sci

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Introduction: It has been aimed to analyze the role of pathogenic effects of mutation and expression anomalies occurring on diaphanous-related formin 1 (DIAPH1), WASP actin nucleation-promoting factor (WASP), myosin heavy chain 9 (MYH9), actinin alpha 1 (ACNT1), filamin A (FLNA), and tubulin beta 1 class VI (TUBB1), which are known as fundamental cellular skeleton proteins, on the development and progression of cancer via bioinformatic tools. Methods: The genome sequence and expression profiles of 594 Colorectal Cancer (CRC) patients were obtained via bioinformatic tools, which provide data for The Cancer Genome Atlas. The mutation patterns of six genes were determined in detail, and for the prediction of pathogenic properties of identified changes for CRC, Polymorphism Phenotyping v2, Screening for Non-Acceptable Polymorphisms, and the Catalogue Of Somatic Mutations In Can- cer were utilized. Apart from the mutation profile, the effects of existing mutations on messenger ribonucleic acid (mRNA) expression and survival were also identified. Moreover, the Search Tool for the Retrieval of Interacting Genes/Proteins network analysis was realized to further comprehend the functional relations of proteins in cellu- lar processes. Results: There have been 142 distinct point mutations, gene amplification, and deep deletions identified on DIAPH1, WAS, MYH9, ACNT1, FLNA, and TUBB1 genes. ACTN1 and FLNA low mRNA expression levels for DIAPH1 increased, and the mRNA expression level was statistically significant (p<0.05). Prognosis-wise, the effect of mRNA expression on survival in the absence of disease was meaningful for FLNA (p=0.011). Discussion and Conclusion: Bioinformatic analysis data in DIAPH1, WASP, MYH9, ACNT1, FLNA, and TUBB1 genes, which are important in CRC pathogenesis revealed in this study, will be a guide for future laboratory studies.

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“…The gene expression level of Diaph1 was elevated in multiple cancers, including cancer of prostate, breast, lung and lymphocyte, 45 and it correlated with the clinical stage of laryngeal squamous cell carcinoma, 16 metastasis of colorectal cancer, 15 and poor overall survival of patients with high grade (class G3) head and neck cancer. 16 Diaph1 inhibited the apoptosis of cancer cells 16 and promoted cancer cell adhesion, invasion, and metastasis in vitro. 15 , 45 Additionally, the knockdown of Diaph1 in HCT116 colorectal cancer cells reduced lung metastasis in a metastasis mouse model.…”

Section: Discussionmentioning

confidence: 99%

Protein diaphanous homolog 1 (Diaph1) promotes myofibroblastic activation of hepatic stellate cells by regulating Rab5a activity and TGFβ receptor endocytosis

Liu

Wang

et al. 2020

FASEB j.

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TGFβ induces the differentiation of hepatic stellate cells (HSCs) into tumor‐promoting myofibroblasts but underlying mechanisms remain incompletely understood. Because endocytosis of TGFβ receptor II (TβRII), in response to TGFβ stimulation, is a prerequisite for TGF signaling, we investigated the role of protein diaphanous homolog 1 (known as Diaph1 or mDia1) for the myofibroblastic activation of HSCs. Using shRNA to knockdown Diaph1 or SMIFH2 to target Diaph1 activity of HSCs, we found that the inactivation of Diaph1 blocked internalization and intracellular trafficking of TβRII and reduced SMAD3 phosphorylation induced by TGFβ1. Mechanistic studies revealed that the N‐terminal portion of Diaph1 interacted with both TβRII and Rab5a directly and that Rab5a activity of HSCs was increased by Diaph1 overexpression and decreased by Diaph1 knockdown. Additionally, expression of Rab5aQ79L (active Rab5a mutant) increased whereas the expression of Rab5aS34N (inactive mutant) reduced the endosomal localization of TβRII in HSCs compared to the expression of wild‐type Rab5a. Functionally, TGFβ stimulation promoted HSCs to express tumor‐promoting factors, and α‐smooth muscle actin, fibronection, and CTGF, markers of myofibroblastic activation of HSCs. Targeting Diaph1 or Rab5a suppressed HSC activation and limited tumor growth in a tumor implantation mouse model. Thus, Dipah1 and Rab5a represent targets for inhibiting HSC activation and the hepatic tumor microenvironment.

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DIAPH1 Is Upregulated and Inhibits Cell Apoptosis through ATR/p53/Caspase-3 Signaling Pathway in Laryngeal Squamous Cell Carcinoma

Cited by 27 publications

References 29 publications

Bioinformatics analysis of laryngeal squamous cell carcinoma: seeking key candidate genes and pathways

Bioinformatics analysis of laryngeal squamous cell carcinoma: seeking key candidate genes and pathways

Why Cytoskeletal Associated Proteins are Important in Colorectal Cancer Patients: Molecular & Bioinformatic Analysis

Protein diaphanous homolog 1 (Diaph1) promotes myofibroblastic activation of hepatic stellate cells by regulating Rab5a activity and TGFβ receptor endocytosis

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