Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma in adulthood, comprises multiple biologically and clinically distinct subtypes including germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) DLBCL. Gene expression profile studies have shown that its most aggressive subtype, ABC-DLBCL, is associated with constitutive activation of the NF-kappaB transcription complex. However, except for a small fraction of cases, it remains unclear whether NF-kappaB activation in these tumours represents an intrinsic program of the tumour cell of origin or a pathogenetic event. Here we show that >50% of ABC-DLBCL and a smaller fraction of GCB-DLBCL carry somatic mutations in multiple genes, including negative (TNFAIP3, also called A20) and positive (CARD11, TRAF2, TRAF5, MAP3K7 (TAK1) and TNFRSF11A (RANK)) regulators of NF-kappaB. Of these, the A20 gene, which encodes a ubiquitin-modifying enzyme involved in termination of NF-kappaB responses, is most commonly affected, with approximately 30% of patients displaying biallelic inactivation by mutations and/or deletions. When reintroduced in cell lines carrying biallelic inactivation of the gene, A20 induced apoptosis and cell growth arrest, indicating a tumour suppressor role. Less frequently, missense mutations of TRAF2 and CARD11 produce molecules with significantly enhanced ability to activate NF-kappaB. Thus, our results demonstrate that NF-kappaB activation in DLBCL is caused by genetic lesions affecting multiple genes, the loss or activation of which may promote lymphomagenesis by leading to abnormally prolonged NF-kappaB responses.
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PMID:Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. 1941 64

MicroRNA (miRNA) is a family of small regulatory RNAs that post-transcriptionally regulate many biological functions including growth and development. Recently, the expression of chicken miRNA miR-143 was identified by using a deep sequencing approach. In other vertebrate species, miR-143 functions as a regulator of adipocyte differentiation and as a tumour suppressor. However, little is known about the biological function(s) of miR-143 in chickens. To study the functions of chicken miR-143, DNA microarray analysis and a dual luciferase reporter assay were employed to identify genes directly targeted by miR-143 as well as other biologically relevant genes. Microarray analysis indicated that 124 genes were differentially expressed upon in vitro anti-miR-143 treatment in embryonic chick splenocytes (P-value cutoff <0.01). Many of these genes are associated with cell proliferation, apoptosis and tumourigenesis. Six of the up-regulated genes possess at least one potential miR-143 binding site in their 3'UTRs, of these the binding sites of PYCR2, PSTPIP1 and PDCD5 were validated by an in vitro luciferase reporter assay. In addition, several potential targets with important biological functions were identified by the miRanda algorithm and experimentally confirmed. These targets include KLF5, MAP3K7, TARDBP and UBE2E3, which have conserved miR-143 binding sites across multiple vertebrate species. Potential chicken specific miR-143 target sites were also validated for LPIN1, PCK2, PYCR2, METTL14, SLC2A2 and TNFSF10. Overall, the current study suggests that miR-143 is ubiquitously expressed among tissues and is likely to be involved in the regulation of cell proliferation and apoptosis.
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PMID:Identification of target genes and pathways associated with chicken microRNA miR-143. 2006 47