Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P42345 (mTOR)
 26,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that circular RNA (circRNA) is associated with human cancer. However, few studies have been reported in active pulmonary tuberculosis (APTB). The global circRNA expression was detected in the peripheral blood mononuclear cells (PBMCs) of APTB patients (n=5) and health controls (HC) (n=5) by using high-throughput sequencing. According to the systematical bioinformatics analysis, the basic content of circRNAs and their fold changes in the two groups were calculated. We selected 6 significant differentially expressed circRNAs, hsa_circ_0005836, hsa_circ_0009128, hsa_circ_0003519, hsa_circ_0023956, hsa_circ_0078768, and hsa_circ_0088452 and validated the expression in PBMCs from APTB (n=10) and HC (n=10) by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Further, the verification of these specific circRNAs (hsa_circ_0005836 and hsa_circ_0009128) between APTB (n=34) and HC (n=30) in PBMCs was also conducted by qRT-PCRs. The RNA-seq data showed the significant differential expression of the 523 circRNAs between the APTB and HC groups (199 circRNAs were significantly up-regulated and 324 circRNAs were down-regulated). Hsa_circ_0005836 and hsa_circ_0009128 expression was significantly down-regulated in the PBMCs of APTB (P<0.05) in the samples of APTB compared to HC in our study. The gene ontology based enrichment analysis of the circRNA-miRNA-mRNAs network showed that cellular catabolic process (P=7.10E-08), regulation of metabolic process (P=2.10E-06), catalytic activity (P=3.67E-08), protein binding (P=1.71E-07), cell part (P=3.46E-06), intracellular part (P=1.71E-07), and intracellular (P=3.67E-08) were recognized in the comparisons between APTB and HC. Based on KEGG analysis, HTLV-I infection, regulation of actin cytoskeleton, neurotrophin signaling pathway and mTOR signaling pathway were relevant during tuberculosis bacillus infection. We found for the first time that hsa_circ_0005836 and hsa_circ_0009128 were significantly down-regulated in the PBMCs of APTB compared with HC. Our findings indicate hsa_circ_0005836 might serve as a novel potential biomarker for TB infection.
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PMID:The circular RNA of peripheral blood mononuclear cells: Hsa_circ_0005836 as a new diagnostic biomarker and therapeutic target of active pulmonary tuberculosis. 2884 24

This study aimed to investigate the exact function of RGC-32 in kidney diseases and explore the potential mechanism of RGC-32 in regulating cell cycle. RGC-32 knockout (RGC-32-/-) mice were generated from C57BL/6 embryonic stem cells. Differentially expressed proteins in the kidney were investigated with the isobaric tags for relative and absolute quantification (iTRAQ) technique. Gene ontology analyses (GO), Kyoto encyclopedia of genes and genomes (KEGG) pathway mapping analysis and functional network analysis were also performed. The expressions of Smc3, Smad 2-3, DNA-PK were further confirmed by qPCR. Results showed that 4690 proteins were quantified on the basis of 25165 unique peptides. Comparative proteomic analysis revealed 361 differentially expressed proteins in RGC-32-/- mice (knockout/wild ratio >+/- 1.2 and P<0.05). GO and KEGG pathway mapping analyses showed differentially expressed proteins were involved in spliceosome, fluid shear stress and atherosclerosis protein processing in endoplasmic reticulum, pathways in cancer, viral carcinogenesis, epithelial cell signaling in Helicobacter pylori infection, HTLV-I infection, PI3K-Akt signaling pathway, ubiquitin mediated proteolysis, Parkinson's disease, MAPK signaling pathway, carbon metabolism, Alzheimer's disease, NOD-like receptor signaling pathway, tight junction, Proteoglycans in cancer, phagosome, ribosome, mTOR signaling pathway, and AMPK signaling pathway. Differentially expressed proteins Smc3 (0.821), DNA-PK (0.761), Smad 2-3 (0.631) were involved in cell cycle regulation. mRNA expression of Smad2-3, DNA-PK, and Smc3 was consistent with that from iTRAQ. It is concluded that RGC-32 may affect the expression of many proteins (76 up-regulated and 285 down-regulated) in the kidney, and may regulate the expression of Smc3, DNA-PK and Smad 2-3 to affect the cell cycle.
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PMID:Renal proteomic analysis of RGC-32 knockout mice reveals the potential mechanism of RGC-32 in regulating cell cycle. 2963 74

Bladder cancer is the most common malignant tumor of the urinary system, and it has high incidence, high degree of malignancy, and easy recurrence after surgery. The etiology and pathogenesis of bladder cancer are not fully understood, but more and more studies have shown that its development may be regulated by some core molecules. To identify key molecules in bladder cancer, we constructed a three-layer network by merging lncRNA-miRNA regulatory network, miRNA-mRNA regulatory network, and lncRNA-mRNA coexpression network, and further analyzed the topology attributes of the network including the degree, betweenness centrality and closeness centrality of nodes. We found that miRNA-93 and miRNA-195 are controllers for a three-layer network and regulators of numerous target genes associated with bladder cancer. Functional enrichment analysis of their target mRNAs revealed that miRNA-93 and miRNA-195 may be closely related to bladder cancer by disturbing the homeostasis of the cell cycle or HTLV-I infection. In addition, since E2F1 and E2F2 are enriched in various KEGG signaling pathways, we conclude that they are important target genes of miRNA-93, and participate in the apoptotic process by forming a complex with a certain protein or transcription factor activity, sequence-specific DNA binding in bladder cancer. Similarly, AKT3 is an important target gene of miRNA-195, its expression is associated with PI3K-Akt-mTOR signaling pathway and AMPK-mTOR signaling pathway. Therefore, we speculate that AKT3 may participate in proliferation and apoptosis of bladder cancer cells through these pathways, and ultimately affect the biological behavior of tumor cells. Furthermore, through survival analysis, we found that miRNA-195 and miRNA-93 are associated with poor prognosis of bladder cancer. And the Kaplan-Meier curve showed that 24 mRNAs and nine lncRNAs are closely related to overall survival of bladder cancer.
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PMID:Identification of the Key Factors Related to Bladder Cancer by lncRNA-miRNA-mRNA Three-Layer Network. 3204 16