Bioinformatics Analysis Identifies p53 as a Candidate Prognostic Biomarker for Neuropathic Pain

Gao, Yibo; Sun, Na; Wang, Lieju; Wu, Ying; Ma, Longfei; Hong, Juncong; Ren, Jinxuan; Zhu, Bingquan; Lu, Yu; Yan, Min

doi:10.3389/fgene.2018.00320

Cited by 23 publications

(23 citation statements)

References 44 publications

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“…Spinal cord cell apoptosis reported is observed during the development of neuropathic pain [18,19]. Whiteside et al [40] found that the development of chronic constriction injury-induced neuropathic pain is associated with increased apoptosis in spinal cord cells, which is thought to be the cause of pain.…”

Section: Discussionmentioning

confidence: 99%

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Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis

Deng

Yang

Xie

et al. 2020

Mediators of Inflammation

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Neuropathic pain is a serious clinical problem to be solved. This study is aimed at investigating protein kinase A (PKA) expression in neuropathic pain and its possible mechanisms of involvement. A neuropathic pain-related gene expression dataset was downloaded from Gene Expression Omnibus, and differentially expressed genes were screened using the R software. cytoHubba was used to screen for hub genes. A spared nerve injury (SNI) rat model was established, and the paw withdrawal threshold was determined using von Frey filaments. Western blotting and immunofluorescence were used to detect the expression and cellular localization, respectively, of key proteins in the spinal cord. Western blot, ELISA, and TUNEL assays were used to detect cell signal transduction, inflammation, and apoptosis, respectively. Pka was identified as a key gene involved in neuropathic pain. After SNI, mechanical allodynia occurred, PKA expression in the spinal cord increased, the p38MAPK pathway was activated, and spinal cord inflammation and apoptosis occurred in rats. PKA colocalized with neurons, astrocytes, and microglia, and apoptotic cells were mainly neurons. Intrathecal injection of a PKA inhibitor not only relieved mechanical hyperalgesia, inflammatory reaction, and apoptosis in SNI rats but also inhibited p38MAPK pathway activation. However, intrathecal injection of a p38MAPK inhibitor attenuated mechanical hyperalgesia, inflammation, and apoptosis, but did not affect PKA expression. In conclusion, PKA is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

“…In neuropathic pain, spinal cord cells can undergo apoptosis [18,19], which is closely related to the p38 MAPK pathway [20,21]. Therefore, we hypothesized that PKA is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis

Deng

Yang

Xie

et al. 2020

Mediators of Inflammation

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“…Spinal cord cell apoptosis reportedly is observed during the development of neuropathic pain [17,18].…”

Section: Discussionmentioning

confidence: 99%

“…In neuropathic pain, spinal cord cells can undergo apoptosis [17,18], and apoptosis is closely related to the p38 MAPK pathway [19,20]. Therefore, we hypothesized that PKA is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Protein kinase A is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis

Deng

Yang

Xie

et al. 2019

Preprint

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Background: Neuropathic pain is a serious clinical problem to be solved. Protein kinase A (PKA) is widely distributed in the central nervous system and participates in various signal transduction pathways to regulate cell proliferation and apoptosis. However, it is unclear whether PKA is involved in neuropathic pain. This study aimed to investigate PKA expression in neuropathic pain and its possible mechanisms of involvement. Methods: The mRNA expression dataset of neuropathic pain (GSE24982) was downloaded from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) were screened using the R software. DEGs were subjected to Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. A protein-protein interaction network was constructed using the STRING database, and the Cytoscape plug-in cytoHubba was used to screen for hub genes. A spared nerve injury (SNI) rat model was established and the paw withdrawal threshold was determined using von Frey filaments. Western blotting and immunofluorescence were used to detect the expression and cellular localization of key proteins in the spinal cord, respectively. Western blotting, ELISA, and TUNEL assays were used to detect cell signal transduction, inflammation, and apoptosis, respectively. Results: Among 449 DEGs and 20 hub genes, PKA was identified as a key gene involved in neuropathic pain. After SNI, mechanical allodynia occurred, PKA expression in the spinal cord increased, the p38MAPK pathway was activated, and spinal cord inflammation and apoptosis occurred in rats. Immunofluorescence staining showed that PKA colocalized with neurons, astrocytes, and microglia, and TUNEL with GFAP, Iba-1, Neun double labeling showed that apoptotic cells were mainly neurons. Intrathecal injection of a PKA inhibitor not only relieved mechanical hyperalgesia, inflammatory reaction, and apoptosis in SNI rats, but also inhibited p38MAPK pathway activation. Intrathecal injection of a p38MAPK inhibitor attenuated mechanical hyperalgesia, inflammatory reaction, and apoptosis, but did not affect PKA expression. Conclusions: PKA is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis. This study provides novel insights that my aid in the elucidation of the pathogenesis of neuropathic pain.

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“…The basic properties of differentially expressed proteins were analyzed using Gene Ontology (GO) and protein-protein interaction network at Metascape (https://metascape.org/gp/ index.html) and STRING (https://string-db.org/), respectively (23,24).…”

Section: Bioinformatics Analysismentioning

confidence: 99%

Isobaric Tags for Relative and Absolute Quantitation in Proteomic Analysis of Potential Biomarkers in Invasive Cancer, Ductal Carcinoma In Situ, and Mammary Fibroadenoma

Zhang

Niu

et al. 2020

Front. Oncol.

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Objectives: Breast malignancy is a serious threat to women's health around the world. Following the rapid progress in the field of cancer diagnostics and identification of pathological markers, breast tumor treatment methods have been greatly improved. However, for invasive, ductal carcinomas and mammary fibroadenoma, there is an urgent demand for better breast tumor-linked biomarkers. The current study was designed to identify diagnostic and/or therapeutic protein biomarkers for breast tumors. Methods: A total of 140 individuals were included, comprising 35 healthy women, 35 invasive breast cancers (IBC), 35 breast ductal carcinomas in situ (DCIS), and 35 breast fibroadenoma patients. Isobaric tags for relative and absolute quantitation (iTRAQ) proteomic analysis was employed to characterize differentially expressed proteins for potential biomarkers in IBC, DCIS, and fibroadenomas by comparisons with their matched adjacent tissues and/or normal breast tissues. The public databases Metascape and String were used for bioinformatic analyses.

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Bioinformatics Analysis Identifies p53 as a Candidate Prognostic Biomarker for Neuropathic Pain

Cited by 23 publications

References 44 publications

Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis

Protein Kinase A Is Involved in Neuropathic Pain by Activating the p38MAPK Pathway to Mediate Spinal Cord Cell Apoptosis

Protein kinase A is involved in neuropathic pain by activating the p38MAPK pathway to mediate spinal cord cell apoptosis

Isobaric Tags for Relative and Absolute Quantitation in Proteomic Analysis of Potential Biomarkers in Invasive Cancer, Ductal Carcinoma In Situ, and Mammary Fibroadenoma

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