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

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.

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Screening for differentially expressed circRNAs in ischemic stroke by RNA sequencing

BMC Neurology ◽

10.1186/s12883-021-02397-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Duncan Wei ◽

Jian Chen ◽

Xiaopu Chen ◽

Shaoyan Wu ◽

Zhaolin Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Signaling Pathway ◽

Rna Sequencing ◽

Cell Receptor ◽

Differentially Expressed ◽

Receptor Signaling ◽

Qrt Pcr ◽

Receptor Signaling Pathway ◽

Cell Receptor Signaling ◽

Host Genes

Abstract Background Ischemic stroke is a disease with high rate of death and disability worldwide. CircRNAs, as a novel type of non-coding RNAs, lacking 5’ caps and 3’ poly-A tails, has been associated with ischemic stroke. This study aimed to investigate key circRNAs related to ischemic stroke. Methods RNA sequencing was performed obtain the circRNA expression profiles from peripheral whole blood of three ischemic stroke patients and three healthy individuals. Through bioinformatic analysis, differentially expressed circRNAs (DEcircRNAs) were identified, and GO and pathway analyses for the host genes of DEcircRNAs were conducted. The expression levels of selected circRNAs were analyzed with qRT-PCR. To further explore the functions of key circRNAs, a DEcircRNA-miRNA interaction network was constructed. Results A total of 736 DEcircRNAs were detected in ischemic stroke. Functional annotation of host genes of DEcircRNAs revealed several significantly enriched pathways, including Fc epsilon RI signaling pathway, B cell receptor signaling pathway, and T cell receptor signaling pathway. The qRT-PCR results were largely in keeping with our RNA-seq data. The ROC curve analyses indicated that hsa_circ_0000745, hsa_circ_0001459, hsa_circ_0003694 and hsa_circ_0007706 with relatively high diagnostic value. A circRNA-miRNA network, including 1544 circRNA-miRNA pairs, 456 circRNAs and 4 miRNAs, was obtained. Conclusions The results of our study may help to elucidate the specific mechanism underlying ischemic stroke.

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Upregulation of T Cell Receptor Signaling Pathway Components in Gestational Diabetes Mellitus Patients: Joint Analysis of mRNA and circRNA Expression Profiles

Frontiers in Endocrinology ◽

10.3389/fendo.2021.774608 ◽

2022 ◽

Vol 12 ◽

Author(s):

Yan-ming Chen ◽

Qiong Zhu ◽

Jie Cai ◽

Zhi-jia Zhao ◽

Bin-bin Yao ◽

...

Keyword(s):

Diabetes Mellitus ◽

T Cell ◽

Signaling Pathway ◽

T Cell Receptor ◽

Cell Receptor ◽

Differentially Expressed ◽

Receptor Signaling ◽

T Cell Receptor Signaling ◽

Receptor Signaling Pathway ◽

Cell Receptor Signaling

ObjectiveGestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and its pathogenesis is still unclear. Studies have shown that circular RNAs (circRNAs) can regulate blood glucose levels by targeting mRNAs, but the role of circRNAs in GDM is still unknown. Therefore, a joint microarray analysis of circRNAs and their target mRNAs in GDM patients and healthy pregnant women was carried out.MethodsIn this study, microarray analyses of mRNA and circRNA in 6 GDM patients and 6 healthy controls were conducted to identify the differentially expressed mRNA and circRNA in GDM patients, and some of the discovered mRNAs and circRNAs were further validated in additional 56 samples by quantitative realtime PCR (qRT-PCR) and droplet digital PCR (ddPCR).ResultsGene ontology and pathway analyses showed that the differentially expressed genes were significantly enriched in T cell immune-related pathways. Cross matching of the differentially expressed mRNAs and circRNAs in the top 10 KEGG pathways identified 4 genes (CBLB, ITPR3, NFKBIA, and ICAM1) and 4 corresponding circRNAs (circ-CBLB, circ-ITPR3, circ-NFKBIA, and circ-ICAM1), and these candidates were subsequently verified in larger samples. These differentially expressed circRNAs and their linear transcript mRNAs were all related to the T cell receptor signaling pathway, and PCR results confirmed the initial microarray results. Moreover, circRNA/miRNA/mRNA interactions and circRNA-binding proteins were predicted, and circ-CBLB, circ-ITPR3, and circ-ICAM1 may serve as GDM-related miRNA sponges and regulate the expression of CBLB, ITPR3, NFKBIA, and ICAM1 in cellular immune pathways.ConclusionUpregulation of T cell receptor signaling pathway components may represent the major pathological mechanism underlying GDM, thus providing a potential approach for the prevention and treatment of GDM.

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

Immunity ◽

10.1016/j.immuni.2006.11.008 ◽

2007 ◽

Vol 26 (1) ◽

pp. 55-66 ◽

Cited By ~ 59

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

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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 ◽

10.1182/blood.v126.23.5289.5289 ◽

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.

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