scholarly journals Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Lin Luo ◽  
Wen-Hua Zhou ◽  
Jiang-Jia Cai ◽  
Mei Feng ◽  
Mi Zhou ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
Diabetic Peripheral Neuropathy ◽  
Cell Receptor ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Receptor Signaling ◽  
Major Mechanism ◽  
Receptor Signaling Pathway ◽  
Neurotrophin Signaling

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the “neurotrophin-MAPK signaling pathway” was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

scholarly journals Microarray Analysis of Long Noncoding RNAs in Female Diabetic Peripheral Neuropathy Patients

2018 ◽  
Vol 46 (3) ◽  
pp. 1209-1217 ◽  
Author(s):  
Lin Luo ◽  
Lin-Dan Ji ◽  
Jiang-Jia Cai ◽  
Mei Feng ◽  
Mi Zhou ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
Microarray Analysis ◽  
Diabetic Peripheral Neuropathy ◽  
Relevant Information ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Differentially Expressed ◽  
Qrt Pcr ◽  
Kegg Pathway Analysis

Background/Aims: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus (DM). Because of its controversial pathogenesis, DPN is still not diagnosed or managed properly in most patients. Methods: In this study, human lncRNA microarrays were used to identify the differentially expressed lncRNAs in DM and DPN patients, and some of the discovered lncRNAs were further validated in additional 78 samples by quantitative realtime PCR (qRT-PCR). Results: The microarray analysis identified 446 and 1327 differentially expressed lncRNAs in DM and DPN, respectively. The KEGG pathway analysis further revealed that the differentially expressed lncRNA-coexpressed mRNAs between DPN and DM groups were significantly enriched in the MAPK signaling pathway. The lncRNA/mRNA coexpression network indicated that BDNF and TRAF2 correlated with 6 lncRNAs. The qRT-PCR confirmed the initial microarray results. Conclusion: These findings demonstrated that the interplay between lncRNAs and mRNA may be involved in the pathogenesis of DPN, especially the neurotrophin-MAPK signaling pathway, thus providing relevant information for future studies.

scholarly journals Comprehensive Analysis of the Immune and Prognostic Implication of MMP14 in Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Chun-long Zheng ◽  
Qiang Lu ◽  
Nian Zhang ◽  
Peng-yu Jing ◽  
Ji-peng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Cell Receptor ◽  
Risk Scores ◽  
Pathway Enrichment Analysis ◽  
Receptor Signaling ◽  
Immune Infiltration ◽  
Receptor Signaling Pathway

More and more studies have indicated an association between immune infiltration in lung cancer and clinical outcomes. Matrix metalloproteinase 14 (MMP14) has been reported to be dysregulated in many types of tumors and involved in the development and progression of tumors. However, its contribution to cancer immunity was rarely reported. In the study, we found that MMP14 expression was distinctly upregulated in lung cancer specimens compared with nontumor lung specimens. High MMP14 expression predicted a poor prognosis of lung squamous cell carcinoma (LUSC) patients. Increased MMP14 expressions were observed to be positively related to high immune infiltration levels in most of the immune cells. A pathway enrichment analysis of 32 MMP14-associated immunomodulators indicated the involvement of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Based on MMP14-associated immunomodulators, we applied multivariate assays to construct multiple-gene risk prediction signatures. We observed that risk scores were independently associated with overall survival. These data highlighted that MMP14 was involved in tumor immunity, indicating that MMP14 could serve as a novel prognostic biomarker and therapeutic target for lung cancer. Our data suggest that the four genes identified in this study may serve as valuable biomarkers of lung cancer patient outcomes.

scholarly journals Identification of Key mRNAs and lncRNAs in Neonatal Sepsis by Gene Expression Profiling

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Lin Bu ◽  
Zi-wen Wang ◽  
Shu-qun Hu ◽  
Wen-jing Zhao ◽  
Xiao-juan Geng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neonatal Sepsis ◽  
Ribosome Biogenesis ◽  
Cell Lineage ◽  
Cell Receptor ◽  
Rna Degradation ◽  
Receptor Signaling ◽  
Nf Kappa B ◽  
Ppi Networks ◽  
Receptor Signaling Pathway

Neonatal sepsis is one of the most prevalent causes of death of the neonates. However, the mechanisms underlying neonatal sepsis remained unclear. The present study identified a total of 1128 upregulated mRNAs and 1008 downregulated mRNAs, 28 upregulated lncRNAs, and 61 downregulated lncRNAs in neonatal sepsis. Then, we constructed PPI networks to identify key regulators in neonatal sepsis, including ITGAM, ITGAX, TLR4, ITGB2, SRC, ELANE, RPLP0, RPS28, RPL26, and RPL27. lncRNA coexpression analysis showed HS.294603, LOC391811, C12ORF47, LOC729021, HS.546375, HNRPA1L-2, LOC158345, and HS.495041 played important roles in the progression of neonatal sepsis. Bioinformatics analysis showed DEGs were involved in the regulation cellular extravasation, acute inflammatory response, macrophage activation of NF-kappa B signaling pathway, TNF signaling pathway, HIF-1 signaling pathway, Toll-like receptor signaling pathway, and ribosome, RNA transport, and spliceosome. lncRNAs were involved in regulating ribosome, T cell receptor signaling pathway, RNA degradation, insulin resistance, ribosome biogenesis in eukaryotes, and hematopoietic cell lineage. We thought this study provided useful information for identifying novel therapeutic markers for neonatal sepsis.

scholarly journals The CARMA1-Bcl10 Signaling Complex Selectively Regulates JNK2 Kinase in the T Cell Receptor-Signaling Pathway

Immunity ◽  
2007 ◽  
Vol 26 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Marzenna Blonska ◽  
Bhanu P. Pappu ◽  
Reiko Matsumoto ◽  
Hongxiu Li ◽  
Bing Su ◽  
...  
Keyword(s):  
T Cell ◽  
Signaling Pathway ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Receptor Signaling ◽  
Signaling Complex ◽  
T Cell Receptor Signaling ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling

An HSP90 Inhibitor, PU-H71, Antagonizes Stroma-Induced Pro-Survival Effects in CLL through Its Inhibition of Multi-Component B-Cell Receptor Signaling Pathway

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5289-5289
Author(s):  
Ailin Guo ◽  
Pin Lu ◽  
Chaojie Zhen ◽  
Gabriela Chiosis ◽  
Yue Lynn Wang
Keyword(s):  
B Cell ◽  
Signaling Pathway ◽  
Cell Receptor ◽  
Hsp90 Inhibitor ◽  
B Cell Receptor ◽  
Receptor Signaling ◽  
Bcr Signaling ◽  
Receptor Signaling Pathway ◽  
B Cell Receptor Signaling ◽  
Cell Receptor Signaling

Abstract Background: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B-cells in the hematopoietic system. The B-cell receptor (BCR) plays an essential role in the pathogenesis of CLL and many components of the BCR signaling pathway are known clients of HSP90. HSP90 is a highly conserved molecular chaperone that ensures the proper folding and stabilization of its client proteins. In this study, we investigated whether PU-H71 a novel purine-scaffold HSP90 Inhibitor, has anti-tumor activity in CLL by destabilizing BCR signaling pathway constituents. Design: Fresh CLL cells were isolated and cultured ex vivo with or without stromal co-culture. Molecular and cellular events were studied in PU-H71-treated and control CLL cells. Results: Immunoblotting revealed that a significantly higher amount of HSP90 is present in CLL cells than in peripheral blood mononuclear cells (PBMC), suggesting the chaperone is pathogenically relevant. We found that PU-H71 caused the death of CLL cells in a dose and time dependent manner while the viability of either PBMC or normal B lymphocytes were not affected. PU-H71 induced apoptosis resulting in CLL cell death as it caused mitochondrial cytochrome C release and a decrease in the abundance of several anti-apoptotic proteins. Interestingly, PU-H71 has the ability to counteract the pro-survival effects of the stroma and caused apoptosis in CLL cells co-cultured with stroma. To gain mechanistic insights into how PU-H71 acts, we examined the BCR signaling pathway. We found that the amounts of several key components of the pathway were reduced by PU-H71 treatment. This occurred even in the presence of stromal co-culture. The results suggest that PU-H71 antagonizes the function of HSP90 leading to the destabilization of the BCR signaling transducers. A chemical pull-down experiment revealed the co-existence of the BCR components and HSP90 in the same complex, suggesting these BCR constituents are indeed clients of HSP90 in CLL cells. Further, specific genetic knock-down of the signal transducers by siRNA confirmed their key roles in mediating the survival of CLL cells. Conclusions: PU-H71 antagonizes stroma-induced pro-survival effects in CLL through its inhibition of the B-cell receptor signaling pathway. Our results suggest that PU-H71 may serve as a useful therapy against CLL and is worth further clinical development. Disclosures No relevant conflicts of interest to declare.

scholarly journals Identification of potential microRNAs and KEGG pathways in denervation muscle atrophy based on meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Xinyi Gu ◽  
Bo Jin ◽  
Zhidan Qi ◽  
Xiaofeng Yin
Keyword(s):  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Meta Analysis ◽  
Cell Receptor ◽  
Differentially Expressed ◽  
Receptor Signaling ◽  
Denervated Muscle ◽  
Kegg Pathways ◽  
Receptor Signaling Pathway ◽  
Cell Receptor Signaling

AbstractThe molecular mechanism of muscle atrophy has been studied a lot, but there is no comprehensive analysis focusing on the denervated muscle atrophy. The gene network that controls the development of denervated muscle atrophy needs further elucidation. We examined differentially expressed genes (DEGs) from five denervated muscle atrophy microarray datasets and predicted microRNAs that target these DEGs. We also included the differentially expressed microRNAs datasets of denervated muscle atrophy in previous studies as background information to identify potential key microRNAs. Finally, we compared denervated muscle atrophy with disuse muscle atrophy caused by other reasons, and obtained the Den-genes which only differentially expressed in denervated muscle atrophy. In this meta-analysis, we obtained 429 up-regulated genes, 525 down-regulated genes and a batch of key microRNAs in denervated muscle atrophy. We found eight important microRNA-mRNA interactions (miR-1/Jun, miR-1/Vegfa, miR-497/Vegfa, miR-23a/Vegfa, miR-206/Vegfa, miR-497/Suclg1, miR-27a/Suclg1, miR-27a/Mapk14). The top five KEGG pathways enriched by Den-genes are Insulin signaling pathway, T cell receptor signaling pathway, MAPK signaling pathway, Toll-like receptor signaling pathway and B cell receptor signaling pathway. Our research has delineated the RNA regulatory network of denervated muscle atrophy, and uncovered the specific genes and terms in denervated muscle atrophy.

Sign in / Sign up

Export Citation Format

Share Document