Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.60 (caspase-7)
 920 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

microRNAs play an important roles in cell growth, differentiation, proliferation and apoptosis. They can function either as tumor suppressors or oncogenes. We found that the overexpression of miR-192 inhibited cell proliferation in A549, H460 and 95D cells, and inhibited tumorigenesis in a nude mouse model. Both caspase-7 and the PARP protein were activated by the overexpression of miR-192, thus suggesting that miR-192 induces cell apoptosis through the caspase pathway. Further studies showed that retinoblastoma 1 (RB1) is a direct target of miR-192. Over-expression of miR-192 decreased RB1 mRNA and protein levels and repressed RB1-3'-UTR reporter activity. Knockdown of RB1 using siRNA resulted in a similar cell morphology as that observed for overexpression of miR-192. Additionally, RB1-siRNA treatment inhibited cell proliferation and induced cell apoptosis in lung cancer cells. Analysis of miRNA expression in clinical samples showed that miR-192 is significantly downregulated in lung cancer tissues compared to adjacent non-cancerous lung tissues. In conclusion, our results demonstrate that miR-192 is a tumor suppressor that can target the RB1 gene to inhibit cell proliferation and induce cell apoptosis in lung cancer cells. Furthermore, miR-192 was expressed at low levels in lung cancer samples, indicating that it might be a promising therapeutic target for lung cancer treatment.
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PMID:MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells. 2151 13

MicroRNA (miRNA) is a small noncoding RNA molecule, 19-25 nucleotides in length, which regulates several pathways including cell development, cell proliferation, carcinogenesis, apoptosis, etc. In this study, the over-expression of microRNA-205 (miR-205) increased the number of apoptotic cells by at least 4 times compared to the control. In addition, over-expressed miRNA in KB oral cancer cells triggered apoptosis via the caspase cascade, including the cleavage of caspase-9, caspase-7, caspase-3, and PARP. Flow cytometry showed that apoptotic cell death was increased significantly by 35.33% in KB oral cancer cells with over-expressed miR-205 compared to the control. The microarray data showed that axis inhibitor protein 2 (Axin2) was down-regulated in KB oral cancer cells transfected with miR-205. In addition, Axin2 was down-regulated by approximately 50% by over-expressed miR-205 at both the mRNA and protein levels. Interestingly, Axin2 was up-regulated in KB oral cancer compared to human normal oral keratinocytes. Furthermore, the cell cytotoxicity and apoptotic population of KB oral cancer cells were increased significantly after Axin2 siRNA transfection. These results suggest that Axin2 is might be as potential oncogene in KB oral cancer cells. The luciferase assay showed that over-expressed miR-205 in KB oral cancer cells suppressed AXIN2 expression through an interaction with its own binding site at AXIN2 3'UTR (64-92). These results suggest that miR-205 is a novel anti-oncogenic miRNA in KB oral cancer cells, and may have potential applications in oral cancer therapy.
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PMID:MicroRNA-205 suppresses the oral carcinoma oncogenic activity via down-regulation of Axin-2 in KB human oral cancer cell. 2416 97

Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions. The decreased miR-101-3p caused elevated Bim expression by targeting its 3'-untranslated region (3'-UTR). This resulted in activation of the intrinsic pathway of apoptosis via interaction with Bcl-2, decreased mitochondrial membrane potential, cytochrome c release, mitochondrial reactive oxygen species (ROS) production, and caspase activation. These events were abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a determinant role of the miR-101-3p/Bim axis in serum deprivation-induced apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is mediated by both caspase-3 and -1, which are activated by two distinct intrinsic mechanisms, cytochrome c release and ROS-induced inflammasome activation, respectively. In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings provide mechanistic insight into a novel function of miR-101-3p in serum withdrawal-induced apoptosis triggered by activating two different intrinsic or mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target that limits endothelial cell death associated with vascular disorders.
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PMID:A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis. 2851 40

The process of genetically programmed cell death, or apoptosis, plays a crucialrolein cellular homeostasis and gene expression. Disruption of apoptosis may lead to aberrant immune responses, cancer, and neurodegenerative diseases. Single nucleotide polymorphisms (SNPs) present in various microRNA (miRNA) genes and targets being an alteration of miRNA activity resulting in human diseases. Evidence reported that SNPs increase/decrease the effectiveness of the interaction between miRNAs and their target genes associated with diseases. The primary purpose of this study is not only to identify miRSNPs on the CASP7 gene (caspase-7) and SNPs in miRNA genes targeting 3'UTR but also to evaluate the effect of thesegene variations in apoptosis and their associated diseases. We detected 120 miRNAs binding sites and 27 different SNPs in binding sites of miRNA in 3'UTR of the CASP7 gene by ten different online softwares. Interestingly, miR-371b-5p's binding site on CASP7 has an SNP (rs576198588, G/T) on CASP7 3'UTR, and its genomic sequence has an SNP (rs751339395, G/T) at the same nucleotide with rs576198588. Similarly, two other SNPs (rs774879764, C/G rs750389063, C/T) were identified at the first position binding site of miR-371b-5p. Here, miRSNP (rs576198588) at CASP7 3'UTR and SNP (rs751339395) at miR-371b-5p genomic sequence cross-matches at the same site of binding region. Besides, miR-371b-5p targets many apoptosis-related genes (HIP1, TRIAP1, GSKIP, NIN, DAP, CAAP1, XIAP, TMBIM1, TMBIM4, TNFRSF10A, RAD21, AKT1, BAG1, BAG4) even though it had no apoptosis correlated interaction demonstrated formerly. It assures that CASP7 could have a significant consequence on apoptosis through different pathways. Henceforth, this study was representing and signifying an influential connotation among miR-371b-5p and apoptosis via computational exploration and recommended to have better insight.
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PMID:The Relevance of SNPs at 3'UTR Region of CASP7 and miR-371b-5p Associated Diseases: A Computational Analysis. 3295 Nov 55