&lt;p&gt;Progression of the role of CRYAB in signaling pathways and cancers&lt;/p&gt;

Zhang, JunFei; Liu, Jia; Wu, Jiali; Li, Wenfeng; Chen, ZhongWei; Yang, Le-Min

doi:10.2147/ott.s201799

Cited by 69 publications

(66 citation statements)

References 152 publications

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“…We used cell-type marker analysis to identify the most upregulated genes in these clusters and found that these clusters are likely driving the upregulation of iron accumulation and cell stress genes observed in the differential gene expression test described above. Gene expression analysis between conditions once again revealed an increase in iron accumulation genes (FTH1 and FTL (Iancu 1992;Vidal et al 2004)) and a cell stress gene (CRYAB (Ousman et al 2007;Zhang et al 2019)) ( Fig. 3c).…”

Section: Iron Accumulation and Cell Stress In Cte-specific Olsmentioning

confidence: 89%

“…To further understand the gene expression changes that might be driving the observed OL differences in CTE, we tested for differential gene expression between conditions. The most differentially expressed genes between conditions included CRYAB (anti-apoptotic and neuroprotective factor (Zhang et al 2019;Ousman et al 2007;Schirmer et al 2019)) and FTH1 (iron accumulation (Iancu 1992;Vidal et al 2004;Schirmer et al 2019)) ( Fig. 2e).…”

Section: Global Depletion Of Ols In Cte White Mattermentioning

confidence: 97%

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Altered oligodendroglia and astroglia in chronic traumatic encephalopathy

Chancellor

Duke-Cohan

et al. 2020

Preprint

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Chronic traumatic encephalopathy (CTE) is a progressive tauopathy found in contact sport athletes, military veterans, and others exposed to repetitive head injury (McKee et al. 2009(McKee et al. , 2013(McKee et al. , 2016Omalu et al. 2005Omalu et al. , 2006Martland 1928;Critchley 1949). White matter atrophy and axonal loss have been reported in CTE but have not been characterized on a molecular or cellular level (McKee et al. 2013;Holleran et al. 2017;Hsu et al. 2018). Here, we report 24,735 single nucleus RNA-seq profiles from dorsolateral frontal white matter cell nuclei from eight individuals with neuropathologically confirmed CTE and eight age-and sex-matched controls. We identified eighteen transcriptionally distinct nuclei clusters, as well as cell-type-specific differences between conditions. The findings support a global loss of oligodendrocytes (OLs) in CTE, alterations in OL subpopulations, and suggest pathological iron accumulation in OL subpopulations. Total astrocyte number was not different between CTE and controls but showed upregulation of transcripts associated with neuroinflammation. These findings provide novel insight into the molecular and cellular underpinnings of white matter atrophy in CTE, which may lead to an improved understanding of the disease pathogenesis.

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Section: Iron Accumulation and Cell Stress In Cte-specific Olsmentioning

confidence: 89%

Section: Global Depletion Of Ols In Cte White Mattermentioning

confidence: 97%

Altered oligodendroglia and astroglia in chronic traumatic encephalopathy

Chancellor

Duke-Cohan

et al. 2020

Preprint

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“…WGCNA is a powerful tool for analysing multiple genes in large-scale datasets. It has been extensively used to explore gene co-expression modules and hub genes as potential target biomarkers in many cancers (Foroughi et al, 2018;Chen et al, 2018;Giulietti et al, 2016;Liu et al, 2019;Wang et al, 2019a;Wang et al, 2019b;Xu et al, 2018;Zhai et al, 2019;Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). In the current study, we applied WGCNA and systematically identified the turquoise module as the most significantly negatively associated (r = −0.2, P = 4e−04) with pathologic stage for the first time.…”

Section: Discussionmentioning

confidence: 99%

“…Another study (Ding et al, 2019) have also reported that the pseudopodium-enriched atypical kinase 1-PPP1R12B axis inhibits colorectal tumourigenesis and metastasis through the deactivation of the Grb2/PI3K/Akt pathway, which might provide a novel therapeutic strategy for CRC treatment. The hub gene CFD was identified and validated as a potential target gene in papillary thyroid cancer (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). CRYAB is a very important protein involved in a variety of signal transduction pathways, including apoptosis, inflammation and oxidative stress (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c).…”

Section: Discussionmentioning

confidence: 99%

“…The hub gene CFD was identified and validated as a potential target gene in papillary thyroid cancer (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). CRYAB is a very important protein involved in a variety of signal transduction pathways, including apoptosis, inflammation and oxidative stress (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c). CRYAB is a member of the small heat shock protein family (Zhang et al, 2019a;Zhang et al, 2019b;Zhang et al, 2019c), and many studies have confirmed that CRYAB plays an important role in a variety of tumours, such as OSCC (Annertz et al, 2014), colorectal cancer (Li et al, 2017), breast cancer (Kim et al, 2011), and hepatocellular carcinoma (Tang et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

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Identification and validation of key modules and hub genes associated with the pathological stage of oral squamous cell carcinoma by weighted gene co-expression network analysis

Sun

Shi

et al. 2020

PeerJ

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Background Oral squamous cell carcinoma (OSCC) is a major lethal malignant cancer of the head and neck region, yet its molecular mechanisms of tumourigenesis are still unclear. Patients and methods We performed weighted gene co-expression network analysis (WGCNA) on RNA-sequencing data with clinical information obtained from The Cancer Genome Atlas (TCGA) database. The relationship between co-expression modules and clinical traits was investigated by Pearson correlation analysis. Furthermore, the prognostic value and expression level of the hub genes of these modules were validated based on data from the TCGA database and other independent datasets from the Gene Expression Omnibus (GEO) database and the Human Protein Atlas database. The significant modules and hub genes were also assessed by functional analysis and gene set enrichment analysis (GSEA). Results We found that the turquoise module was strongly correlated with pathologic T stage and significantly enriched in critical functions and pathways related to tumourigenesis. PPP1R12B, CFD, CRYAB, FAM189A2 and ANGPTL1 were identified and statistically validated as hub genes in the turquoise module and were closely implicated in the prognosis of OSCC. GSEA indicated that five hub genes were significantly involved in many well-known cancer-related biological functions and signaling pathways. Conclusion In brief, we systematically discovered a co-expressed turquoise module and five hub genes associated with the pathologic T stage for the first time, which provided further insight that WGCNA may reveal the molecular regulatory mechanism involved in the carcinogenesis and progression of OSCC. In addition, the five hub genes may be considered candidate prognostic biomarkers and potential therapeutic targets for the precise early diagnosis, clinical treatment and prognosis of OSCC in the future.

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In high‐grade ovarian carcinoma, platinum‐sensitive tumor recurrence and acquired‐resistance derive from quiescent residual cancer cells that overexpress CRYAB, CEACAM6, and SOX2

Manoir

Delpech

Orsetti

et al. 2022

The Journal of Pathology

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Most high‐grade ovarian carcinomas (HGOCs) are sensitive to carboplatin (CBP)‐based chemotherapy but frequently recur within 24 months. Recurrent tumors remain CBP‐sensitive and acquire resistance only after several treatment rounds. Recurrences arise from a small number of residual tumor cells not amenable to investigation in patients. We developed patient‐derived xenografts (PDXs) that allow the study of these different stages of CBP‐sensitive recurrence and acquisition of resistance. We generated PDX models from CBP‐sensitive and intrinsically resistant HGOC. PDXs were CBP‐ or mock‐treated and tumors were sampled, after treatment and at recurrence. We also isolated models with acquired‐resistance from CBP‐sensitive PDXs. Tumors were characterized at the histological and transcriptome levels. PDX models reproduced treatment response seen in the patients. CBP‐sensitive residual tumors contained nonproliferating tumor cell clusters embedded in a fibrotic mesh. In nontreated PDX tumors and treated CBP‐resistant tumors, fibrotic tissue was not prevalent. Residual tumors had marked differences in gene expression when compared to naïve and recurrent tumors, indicating downregulation of the cell cycle and proliferation and upregulation of interferon response and the epithelial–mesenchymal transition. This gene expression pattern resembled that described in embryonal diapause and ‘drug‐tolerant persister’ states. Residual and acquired‐resistance tumors share the overexpression of three genes: CEACAM6, CRYAB, and SOX2. Immunostaining analysis showed strong CEACAM6, CRYAB, and SOX2 protein expression in CBP‐sensitive residual and acquired‐resistance PDX, thus confirming the RNA profiling results. In HGOC PDX, CBP‐sensitive recurrences arise from a small population of quiescent, drug‐tolerant, residual cells embedded in a fibrotic mesh. These cells overexpress CEACAM6, CRYAB, and SOX2, whose overexpression is also associated with acquired resistance and poor patient prognosis. CEACAM6, CRYAB, and SOX2 may thus serve as a biomarker to predict recurrence and emergence of resistant disease in CBP‐treated HGOC patients. © 2022 The Pathological Society of Great Britain and Ireland.

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<p>Progression of the role of CRYAB in signaling pathways and cancers</p>

Cited by 69 publications

References 152 publications

Altered oligodendroglia and astroglia in chronic traumatic encephalopathy

Altered oligodendroglia and astroglia in chronic traumatic encephalopathy

Identification and validation of key modules and hub genes associated with the pathological stage of oral squamous cell carcinoma by weighted gene co-expression network analysis

In high‐grade ovarian carcinoma, platinum‐sensitive tumor recurrence and acquired‐resistance derive from quiescent residual cancer cells that overexpress CRYAB, CEACAM6, and SOX2

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