DHRSX, A Novel Non-Classical Secretory Protein Associated With Starvation Induced Autophagy

Zhang, Guoying; Luo, Yang; Li, Ge; Wang, Lanlan; Na, Daxiang; Wu, Xiaotong; Zhang, Yingmei; Mo, Xiaoning; Wang, Lu

doi:10.7150/ijms.9529

Cited by 14 publications

(15 citation statements)

References 31 publications

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“…Next, we explored the functions of the hub genes and found that numerous genes were associated with the autophagy process including DEPDC, DHRSX, ATG2A, and C9orf72. These four genes have been reported to be involved in the regulation of autophagy ( Zhang et al, 2014 ; Bakula et al, 2017 ; Wang W. et al, 2020 ; Pang and Hu, 2021 ), and they also showed good classification efficiency in ROC analysis. In addition, DEPDC and DHRSX were highly correlated with NK cell activation.…”

Section: Discussionmentioning

confidence: 91%

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

et al. 2022

Front. Genet.

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Background: Intervertebral disc degeneration (IDD), characterized by diverse pathological changes, causes low back pain (LBP). However, prophylactic and delaying treatments for IDD are limited. The aim of our study was to investigate the gene network and biomarkers of IDD and suggest potential therapeutic targets.Methods: Differentially expressed genes (DEGs) associated with IDD were identified by analyzing the mRNA, miRNA, and lncRNA expression profiles of IDD cases from the Gene Expression Omnibus (GEO). The protein–protein interaction (PPI) network, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis as well as miRNA–lncRNA–mRNA networks were conducted. Moreover, we obtained 71 hub genes and performed a comprehensive analysis including GO, KEGG, gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), Disease Ontology (DO), methylation analysis, receiver operating characteristic (ROC) curve analysis, immune infiltration analysis, and potential drug identification. We finally used qRT-PCR to verify 13 significant DEGs in normal and degenerative nucleus pulposus cells (NPCs).Results: We identified 305 DEGs closely related to IDD. The GO and KEGG analyses indicated that changes in IDD are significantly associated with enrichment of the inflammatory and immune response. GSEA analysis suggested that cell activation involved in the inflammatory immune response amide biosynthetic process was the key for the development of IDD. The GSVA suggested that DNA repair, oxidative phosphorylation, peroxisome, IL-6-JAK-STAT3 signaling, and apoptosis were crucial in the development of IDD. Among the 71 hub genes, the methylation levels of 11 genes were increased in IDD. A total of twenty genes showed a high functional similarity and diagnostic value in IDD. The result of the immune cell infiltration analysis indicated that seven genes were closely related to active natural killer cells. The most relevant targeted hub genes for potential drug or molecular compounds were MET and PIK3CD. Also, qRT-PCR results showed that ARHGAP27, C15orf39, DEPDC1, DHRSX, MGAM, SLC11A1, SMC4, and LINC00887 were significantly downregulated in degenerative NPCs; H19, LINC00685, mir-185-5p, and mir-4306 were upregulated in degenerative NPCs; and the expression level of mir-663a did not change significantly in normal and degenerative NPCs.Conclusion: Our findings may provide new insights into the functional characteristics and mechanism of IDD and aid the development of IDD therapeutics.

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Section: Discussionmentioning

confidence: 91%

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

et al. 2022

Front. Genet.

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“…SGTA, down-regulated in CCM2-KO zebrafish, is not characterized very well but has been shown to interact with 70-kDa heat shock cognate protein and hypothesized to serve housekeeping functions (Liu et al., 1999; Paul et al., 2014). DHRSX, up-regulated only in CCM1 deficient cells, is relatively uncharacterized other than being hypothesized in having a role in positive regulation of starvation-induced autophagy (Zhang et al., 2014). Previous data showed that down-regulation of integrin β4 promotes sphingosylphosphorylcholine-induced autophagy (Ge et al., 2011), suggesting that perturbed autophagy can be observed in CCMs.…”

Section: Discussionmentioning

confidence: 99%

Systems-wide analysis unravels the new roles of CCM signal complex (CSC)

Abou‐Fadel

Vasquez

Grajeda

et al. 2019

Heliyon

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A B S T R A C TCerebral cavernous malformations (CCMs) are characterized by abnormally dilated intracranial capillaries that result in increased susceptibility to stroke. Three genes have been identified as causes of CCMs; KRIT1 (CCM1), MGC4607 (CCM2) and PDCD10 (CCM3); one of them is disrupted in most CCM cases. It was demonstrated that both CCM1 and CCM3 bind to CCM2 to form a CCM signaling complex (CSC) to modulate angiogenesis. In this report, we deployed both RNA-seq and proteomic analysis of perturbed CSC after depletion of one of three CCM genes to generate interactomes for system-wide studies. Our results demonstrated a unique portrait detailing alterations in angiogenesis and vascular integrity. Interestingly, only in-direct overlapped alterations between RNA and protein levels were detected, supporting the existence of multiple layers of regulation in CSC cascades. Notably, this is the first report identifying that both β4 integrin and CAV1 signaling are downstream of CSC, conveying the angiogenic signaling. Our results provide a global view of signal transduction modulated by the CSC, identifies novel regulatory signaling networks and key cellular factors associated with CSC.Heliyon 5 (2019) e02899 Protein extraction for HBMVEC cells and zebrafish embryosHBMVEC cells and zebrafish embryos were lysed using a digital sonifier cell disruptor (Branson model 450 with model 102C converter and double step microtip) in ice cold lysis buffer containing 50 mM Tris-HCl (pH 7.5), 150 mM NaCl, 0.5% NP-40 (Sigma), 50 mM sodium fluoride (Sigma), 1 mM PMSF (Sigma), 1 mM dithiothreitol (Invitrogen) and EDTA-free complete protease inhibitor (Roche). The concentration of protein lysates were measure by Qubit assay (Invitrogen) before analysis.

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“…DHRSX gene is a new gene discovered in 2014 at the Xp22.33 and Yp11.2 in the human genome. It has been shown that the protein encoded by this gene is implicated in the positive regulation of starvation induced autophagy [ 54 ].…”

Section: Resultsmentioning

confidence: 99%

New methodology for repetitive sequences identification in human X and Y chromosomes

Touati

Tajouri

Mesaoudi

et al. 2021

Biomedical Signal Processing and Control

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DHRSX, A Novel Non-Classical Secretory Protein Associated With Starvation Induced Autophagy

Cited by 14 publications

References 31 publications

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

Identification of Core Genes and Screening of Potential Targets in Intervertebral Disc Degeneration Using Integrated Bioinformatics Analysis

Systems-wide analysis unravels the new roles of CCM signal complex (CSC)

New methodology for repetitive sequences identification in human X and Y chromosomes

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