Down-regulation of a novel gene, DRLM, in human liver malignancy from 4q22 that encodes a NAP-like protein

Harada, Haruhito; Nagai, Hisaki; Ezura, Yoichi; Yokota, Takashi; Ohsawa, Ikuroh; Yamaguchi, K; Ohue, Chiharu; Tsuneizumi, Michiko; Mikami, Iwao; Terada, Yayoi; Yabe, Aya; Emi, Mitsuru

doi:10.1016/s0378-1119(02)00855-7

Cited by 21 publications

(22 citation statements)

References 17 publications

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“…Several studies have shown that specific miRNAs are aberrantly expressed in malignant HCC cells or tissues compared to non-malignant hepatocytes or tissue [41][42][43][44][45][46][47] . Selected miRNAs such as miR-21, miR-224, miR34a, miR-221/222, miR-106a, and miR-203 are upregulated in HCC compared to benign hepatocellular tumors such as adenomas or focal nodular hyperplasia.…”

Section: Mirnas and Human Hepatocellular Cancer (Hcc)mentioning

confidence: 99%

“…miRNA-122 was reported to be significantly and specifically down-regulated in HCC in humans as well as in rodents [41,42] . Amongst the putative target genes of miR-122 that can be predicted using computational tools, at least three are of interest in tumorigenesis: the gene for N-Myc, which is frequently rearranged in woodchuck liver tumors by woodchuck hepatitis virus [43] , the gene referred to as ''down-regulated in liver malignancy" [44] , and the gene for cyclin G1 [45] . In fact, miR-122 was shown to modulate cyclin G1 expression in HCC-derived cell lines, and an inverse correlation between miR-122a and cyclin G1 expression in primary liver carcinomas was further observed [45] .…”

Section: Mirnas and Human Hepatocellular Cancer (Hcc)mentioning

confidence: 99%

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MicroRNA signatures in liver diseases

Chen¹

2009

WJG

120

118

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MicroRNAs (miRNAs) are an emerging class of highly conserved non-coding small RNAs that regulate gene expression at the post-transcriptional level. It is now clear that miRNAs can potentially regulate every aspect of cellular activity, including differentiation and development, metabolism, proliferation, apoptotic cell death, viral infection and tumorigenesis. Recent studies provide clear evidence that miRNAs are abundant in the liver and modulate a diverse spectrum of liver functions. Deregulation of miRNA expression may be a key pathogenetic factor in many liver diseases including viral hepatitis, hepatocellular cancer and polycystic liver diseases. A clearer understanding of the mechanisms involved in miRNA deregulation will offer new diagnostic and therapeutic strategies to treat liver diseases. Moreover, better understanding of miRNA regulation and identification of tissue-specific miRNA targets employing transgenic/knockout models and/or modulating oligonucleotides will improve our knowledge of liver physiology and diseases.

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Section: Mirnas and Human Hepatocellular Cancer (Hcc)mentioning

confidence: 99%

Section: Mirnas and Human Hepatocellular Cancer (Hcc)mentioning

confidence: 99%

MicroRNA signatures in liver diseases

Chen¹

2009

WJG

120

118

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“…A human homolog of Nap1l5 has been described and is located at 4q22.1 (Harada et al 2002); comparable to the mouse locus, it is found within an intron of HERC3 containing a CpG island. The protein encoded by Nap1l5 contains a region shared by members of the nucleosome assembly family of proteins.…”

Section: Figure 3 Identification and Methylation Analysis Of The Locumentioning

confidence: 99%

Identification of Novel Imprinted Genes in a Genome-Wide Screen for Maternal Methylation

Smith¹,

Dean²,

Konfortova³

et al. 2003

Genome Res.

166

148

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A characteristic of imprinted genes is that the maternal and paternal alleles show differences in methylation. To perform a genome-wide screen for novel imprinted loci, we applied methylation-sensitive representational difference analysis (Me-RDA) to parthenogenetic mouse embryos, to identify differentially methylated regions (DMRs) methylated specifically on the maternal allele. We isolated a total of 26 distinct clones from known and novel DMRs and identified three novel imprinted genes. Nap1l5 is located on proximal chromosome 6 and encodes a protein with homology with nucleosome assembly proteins (NAPs); it has tissue-specific imprinting with expression from the paternal allele. We identified two DMRs on chromosome 15, a chromosome that was not thought to contain imprinted loci, and demonstrated that each is associated with a paternally expressed transcript. Peg13 gives rise to a noncoding RNA that is highly expressed in the brain and imprinted in all tissues examined. A DMR was also identified at the chromosome 15 Slc38a4 gene, which encodes a system A amino acid transporter; we show that Slc38a4 is imprinted in a tissue-specific manner. Interestingly, two of the three novel genes identified in this screen are located within the introns of other genes; their identification indicates that such "microimprinted" domains may be more common than previously thought.

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“…Many important genes encoding albumin, alcohol dehydrogenase (ADH3), fibrinogen and UDPglucuronyltransferase, which are predominantly expressed in the liver, are located on chromosome 4q. Genes on the long arm of this chromosome including protein tyrosine phosphatase, non-receptor type 13 (PTPN13), nucleosome assembly protein 1-like 5 (NAP1L5), and PR domain containing 5 (PRDM5), were documented as potential TSGs [28][29][30] . However, a large number of loci with high LOH frequency found in HCC have not been explored.…”

Section: Discussionmentioning

confidence: 99%

LOH analysis of genes around D4S2964 identifies ARD1B as a prognostic predictor of hepatocellular carcinoma

Huang

Li²,

Zhang³

et al. 2010

WJG

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performed the experiment; Huang GL and Wei RR analyzed the data; Li BK, Yuan YF and Shi M provided samples and clinical information; Zhang HZ pathologically rediagnosed HCC; Li AH provided ultrasound diagnosis of hepatocirrhosis; Huang BJ and Li HH gave vital comments; Li HH designed the primers and probes of SNP microarray; Huang GL, Li HH and Wang HY wrote the paper; Wang HY designed and guided the research. METHODS:Four hundred and forty single nucleotide polymorphisms (SNPs) located at 49 genes around D4S2964 were selected from the National Center for Biotechnology Information website for the SNPs microarray fabrication. LOH of SNPs markers in 112 cases of hepatocellular carcinoma (HCC) tissues and paired adjacent liver tissues were investigated by the SNPs microarray. The correlation between allelic losses with clinicopathological features and overall survival was analyzed. RESULTS:A fine map of LOH of SNPs in genes around D4S2964 was plotted. The average frequency of LOH in genes was 0.39. A correlation between cirrhosis and the FAL index (fractional allelic loss) was found (P = 0.0202). Larger tumor size was found to be significantly associated with LOH in genes ADP-ribosyltransferase 3 (ART3), nucleoporin 54 kDa (NUP54), scavenger receptor class B, member 2 (SCARB2) and coiled-coil domain containing 158 (CCDC158) (P = 0.043, P = 0.019, P = 0.001, P = 0.037, respectively). Kaplan-Meier analysis showed that patients with LOH in ARD1 homolog B (ARD1B) and septin 11 (SEPT11) had a significantly lower survival rate than those with retention (P = 0.021 and P = 0.004, respectively). A Cox regression model suggested that LOH in ARD1B and SEPT11, respectively, were predictors of the overall survival in HCC (P = 0.006 and P = 0.026, respectively). CONCLUSION:LOH in genes around D4S2964 may play an important role in HCC development and progression. LOH in ARD1B and SEPT11 could serve as novel prognostic predictors in HCC patients.

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Down-regulation of a novel gene, DRLM, in human liver malignancy from 4q22 that encodes a NAP-like protein

Cited by 21 publications

References 17 publications

MicroRNA signatures in liver diseases

MicroRNA signatures in liver diseases

Identification of Novel Imprinted Genes in a Genome-Wide Screen for Maternal Methylation

LOH analysis of genes around D4S2964 identifies ARD1B as a prognostic predictor of hepatocellular carcinoma

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