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)

Using arbitrary primed-PCR (AP-PCR), we have identified a novel genetic alteration located at chromosome 11q23.2 and this genetic alteration was common in 38% of the human Wilms tumour samples analysed. Further characterisation by cloning and sequencing of this genomic region revealed that it represents a part of an uncharacterised gene. We have named this gene as Sporadic Kidney Cancer Gene-1 (SKCG-1). Using fluorescence in situ hybridisation (FISH) approach, we established its localisation on the chromosome 11q23.2. Northern analysis revealed the transcript size of SKCG-1 of 2.09 kb and this was further confirmed by full-length cDNA sequence. Sequence analysis revealed an active translation start site (ATG sequence), a polyadenylation signal sequence (AATAAA), and an open reading frame (ORF) encoding a peptide of 124 amino acids in the cDNA sequence of SKCG-1. Analysis of genomic sequence of SKCG-1 revealed a promoter region containing TATA box located at -13 bp upstream of transcription start site. The AP-PCR, SCAR, and Southern blot analyses indicated genomic loss of SKCG-1 in Wilms tumours. The transcript of SKCG-1 was abundantly present in brain, kidney, liver, testis, salivary gland, foetal brain, foetal liver, whereas relatively lower expression in heart, stomach, prostate and no expression in spleen, colon, lung, small intestine, muscle, adrenal gland, uterus, skin, PBL, and bone marrow was detected. The expression of this gene transcript was either very less or undetectable in Wilms and breast tumours compared to their matched uninvolved tissues. Inhibition of SKCG-1 by siRNA resulted in increased cell proliferation of kidney epithelial cells. Based on the presence of two transmembrane regions in its peptide, SKCG-1 has been predicted as a transmembrane protein. Thus, the findings of this study revealed (i) SKCG-1, a new gene located at 11q23.2 and harbouring genetic alteration in Wilms tumours, (ii) the presence of SKCG-1 gene transcripts in various human normal tissues and its lower expression or absence in Wilms and breast tumours indicate that it may be associated with tumour growth suppressor activity, (iii) the presence of an open reading frame in the cDNA sequence of SKCG-1 indicates that it has potential to encode a protein, (iv) increased cell growth by silencing this gene in HEK293 cells further supports a potential role of this gene in growth of kidney epithelial cells. Our findings suggest that SKCG-1 may have a tumour suppressor role, and implicate genetic alteration in this gene as a potential oncogenic pathway and therapeutic target in kidney and breast cancer.
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PMID:SKCG-1: a new candidate growth regulatory gene at chromosome 11q23.2 in human sporadic Wilms tumours. 1662 58

The MITF and SOX10 transcription factors regulate the expression of genes important for melanoma proliferation, invasion and metastasis. Despite growing evidence of the contribution of long noncoding RNAs (lncRNAs) in cancer, including melanoma, their functions within MITF-SOX10 transcriptional programmes remain poorly investigated. Here we identify 245 candidate melanoma associated lncRNAs whose loci are co-occupied by MITF-SOX10 and that are enriched at active enhancer-like regions. Our work suggests that one of these, Disrupted In Renal Carcinoma 3 (DIRC3), may be a clinically important MITF-SOX10 regulated tumour suppressor. DIRC3 depletion in human melanoma cells leads to increased anchorage-independent growth, a hallmark of malignant transformation, whilst melanoma patients classified by low DIRC3 expression have decreased survival. DIRC3 is a nuclear lncRNA that activates expression of its neighbouring IGFBP5 tumour suppressor through modulating chromatin structure and suppressing SOX10 binding to putative regulatory elements within the DIRC3 locus. In turn, DIRC3 dependent regulation of IGFBP5 impacts the expression of genes involved in cancer associated processes and is needed for DIRC3 control of anchorage-independent growth. Our work indicates that lncRNA components of MITF-SOX10 networks are an important new class of melanoma regulators and candidate therapeutic targets that can act not only as downstream mediators of MITF-SOX10 function but as feedback regulators of MITF-SOX10 activity.
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PMID:The MITF-SOX10 regulated long non-coding RNA DIRC3 is a melanoma tumour suppressor. 3188 Oct 17