Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool
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{"title"=>"Novel primate-specific genes, RMEL 1, 2 and 3, with highly restricted expression in melanoma, assessed by new data mining tool", "type"=>"journal", "authors"=>[{"first_name"=>"Josane F.", "last_name"=>"Sousa", "scopus_author_id"=>"7202617764"}, {"first_name"=>"Raul", "last_name"=>"Torrieri", "scopus_author_id"=>"36912092900"}, {"first_name"=>"Rodrigo R.", "last_name"=>"Silva", "scopus_author_id"=>"36912021600"}, {"first_name"=>"Cristiano G.", "last_name"=>"Pereira", "scopus_author_id"=>"23029019100"}, {"first_name"=>"Valeria", "last_name"=>"Valente", "scopus_author_id"=>"35351234400"}, {"first_name"=>"Erico", "last_name"=>"Torrieri", "scopus_author_id"=>"36912161500"}, {"first_name"=>"Kamila C.", "last_name"=>"Peronni", "scopus_author_id"=>"8734513700"}, {"first_name"=>"Waleska", "last_name"=>"Martins", "scopus_author_id"=>"7003800428"}, {"first_name"=>"Nair", "last_name"=>"Muto", "scopus_author_id"=>"36114962200"}, {"first_name"=>"Guilherme", "last_name"=>"Francisco", "scopus_author_id"=>"7004301624"}, {"first_name"=>"Carla Abdo", "last_name"=>"Brohem", "scopus_author_id"=>"14321323400"}, {"first_name"=>"Carlos G.", "last_name"=>"Carlotti", "scopus_author_id"=>"57194555276"}, {"first_name"=>"Silvya S.", "last_name"=>"Maria-Engler", "scopus_author_id"=>"6507026068"}, {"first_name"=>"Roger", "last_name"=>"Chammas", "scopus_author_id"=>"7004122588"}, {"first_name"=>"Enilza M.", "last_name"=>"Espreafico", "scopus_author_id"=>"6604026481"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-78149450632", "sgr"=>"78149450632", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0013510", "pmid"=>"20975957", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "pui"=>"359931128"}, "id"=>"ee382116-8784-3d7c-bc7d-e4fb8b7f8cb5", "abstract"=>"Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.", "link"=>"http://www.mendeley.com/research/novel-primatespecific-genes-rmel-1-2-3-highly-restricted-expression-melanoma-assessed-new-data-minin", "reader_count"=>22, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>7, "Student > Master"=>5, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Researcher"=>3, "Student > Ph. D. Student"=>7, "Student > Master"=>5, "Student > Bachelor"=>2, "Professor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>2, "Medicine and Dentistry"=>4, "Agricultural and Biological Sciences"=>7, "Arts and Humanities"=>2, "Business, Management and Accounting"=>1, "Chemistry"=>1, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>3}, "Arts and Humanities"=>{"Arts and Humanities"=>2}}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/823223"], "description"=>"<p>Relative expression was calculated according to 2<sup>−ΔΔCT</sup> method, using TBP (Tata-box binding protein) as endogenous control and the mean value of the normalized Cts of all nevi samples as reference. cDNA samples derived from keratynocytes (Ker), nevi (N), primary melanoma tumors (P) and melanoma metastasis (M), from different patients (distinguished with a number following the letter N, P or M) were analyzed by Real-Time PCR. Statistical analyses were performed using ANOVA (after log<sub>e</sub> transformation of the data), for RMEL1 and RMEL2, or the Mann–Whitney test for RMEL3. Metastatic samples numbered 79, 81 and 105 are from lymph node metastasis; 50, 80, 93, 95, 96, 108, 113 and 127 from skin metastasis; 106 from lung metastasis and 82, 83, 116 and 129 from visceral metastasis.</p>", "links"=>[], "tags"=>["profiles", "melanoma"], "article_id"=>493574, "categories"=>["Infectious Diseases", "Molecular Biology", "Genetics", "Cancer"], "users"=>["Josane F. Sousa", "Raul Torrieri", "Rodrigo R. Silva", "Cristiano G. Pereira", "Valeria Valente", "Erico Torrieri", "Kamila C. Peronni", "Waleska Martins", "Nair Muto", "Guilherme Francisco", "Carla Abdo Brohem", "Carlos G. Carlotti Jr.", "Silvya S. Maria-Engler", "Roger Chammas", "Enilza M. Espreafico"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013510.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_profiles_of_RMEL1_2_and_3_during_melanoma_progression_/493574", "title"=>"Expression profiles of <i>RMEL1, 2</i> and <i>3</i> during melanoma progression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-10-20 00:59:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/823612"], "description"=>"<p>(<b>A</b>) Genome context of the gene. The numbers indicate the intron and exon lengths in nucleotides. The region in blue represents the longest ORF found, spanning 294 bp and encoding 98 aa. (<b>B</b>) VISTA plot displaying the conservation of the gene in nine species. The upper and lower limits of the box representing each species correspond, respectively, to 100 and 50% of sequence identity. (<b>C</b>) Multiple alignment with ClustalW of the deduced amino acid sequences for the longest AUG-starting ORF of <i>RMEL2</i> in several primate species (for all species, ORFs were deduced from putative transcribed sequences obtained by alignments of the human cDNA BC063324 against the genomic sequences). (<b>D</b>) Diagram showing an RNA secondary structure predicted by RNAz software. Rule indicates RNA length; pointed blue bar indicates a segment predicted to form the hairpin structure shown, and the number is the <i>RNA-class probability</i> (P) of the prediction, considered significant when greater than 0.5.</p>", "links"=>[], "tags"=>["phylogenetic", "products"], "article_id"=>493968, "categories"=>["Infectious Diseases", "Molecular Biology", "Genetics", "Cancer"], "users"=>["Josane F. Sousa", "Raul Torrieri", "Rodrigo R. Silva", "Cristiano G. Pereira", "Valeria Valente", "Erico Torrieri", "Kamila C. Peronni", "Waleska Martins", "Nair Muto", "Guilherme Francisco", "Carla Abdo Brohem", "Carlos G. Carlotti Jr.", "Silvya S. Maria-Engler", "Roger Chammas", "Enilza M. Espreafico"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013510.g005", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structural_organization_phylogenetic_conservation_and_predicted_products_for_RMEL2_Hs_518391_/493968", "title"=>"Structural organization, phylogenetic conservation, and predicted products for <i>RMEL2</i> (Hs.518391).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-10-20 01:06:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/823431"], "description"=>"<p>(<b>A</b>) Genome context of the gene. The longest cDNA (BC038566) suggests a four-exon gene and ESTs (BE386026, BU156136 and BQ217207) suggest two more exons (shaded boxes). Numbers indicate intron and exon lengths in nucleotides. (<b>B</b>) VISTA plot displaying the conservation of the gene in nine species. The upper and lower limits of the box representing each species correspond, respectively, to 100 and 50% of sequence identity. (<b>C</b>) Multiple alignment of the deduced amino acid sequences of the <i>RMEL1</i> longest AUG-starting ORF of several primate species. (for all species, ORFs were deduced from putative transcribed sequences obtained by alignments of the human cDNA BC038566 against the genomic sequences). (<b>D</b>) Diagram of RNA secondary structures predicted by RNAz software. Rule indicates RNA length; pointed blue bars indicate segments predicted to form hairpin structures, and the numbers indicate the <i>RNA-class probability</i> (P), considered significant when greater than 0.5. Predicted RNA secondary structures for two of the segments (indicated by arrow heads) are shown.</p>", "links"=>[], "tags"=>["phylogenetic", "products"], "article_id"=>493785, "categories"=>["Infectious Diseases", "Molecular Biology", "Genetics", "Cancer"], "users"=>["Josane F. Sousa", "Raul Torrieri", "Rodrigo R. Silva", "Cristiano G. Pereira", "Valeria Valente", "Erico Torrieri", "Kamila C. Peronni", "Waleska Martins", "Nair Muto", "Guilherme Francisco", "Carla Abdo Brohem", "Carlos G. Carlotti Jr.", "Silvya S. Maria-Engler", "Roger Chammas", "Enilza M. Espreafico"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013510.g004", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structural_organization_phylogenetic_conservation_and_predicted_products_for_RMEL1_Hs_295012_/493785", "title"=>"Structural organization, phylogenetic conservation, and predicted products for <i>RMEL1</i> (Hs.295012).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-10-20 01:03:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/823786"], "description"=>"<p>(<b>A</b>) Genome context of the gene. ESTs available (BQ420825, CR746619 and BU161974) for the gene suggest the occurrence of four exons separated by large introns. In the opposite strand of the first intron there is an intron-less actin-like gene (<i>ACTLB2</i>). The numbers indicate the intron and exon lengths in nucleotides. (<b>B</b>) VISTA plot displaying the conservation of the gene in nine species. The upper and lower limits of the box representing each species correspond, respectively, to 100 and 50% of sequence identity. (<b>C</b>) Multiple alignment with ClustalW of the deduced amino acid sequences for the longest ORF, which is a primate-conserved AUG-starting ORF, in several primate species (for all species, ORFs were deduced from putative transcribed sequences obtained by alignments of the human EST BQ420825 against the genomic sequences). (<b>D</b>) Diagram of RNA secondary structures predicted by RNAz software. Rule indicates RNA length; pointed blue bars indicate segments predicted to form the hairpin structures shown, and the numbers indicate the <i>RNA-class probability</i> (P) of the prediction, considered significant when greater than 0.5.</p>", "links"=>[], "tags"=>["phylogenetic", "products"], "article_id"=>494136, "categories"=>["Infectious Diseases", "Molecular Biology", "Genetics", "Cancer"], "users"=>["Josane F. Sousa", "Raul Torrieri", "Rodrigo R. Silva", "Cristiano G. Pereira", "Valeria Valente", "Erico Torrieri", "Kamila C. Peronni", "Waleska Martins", "Nair Muto", "Guilherme Francisco", "Carla Abdo Brohem", "Carlos G. Carlotti Jr.", "Silvya S. Maria-Engler", "Roger Chammas", "Enilza M. Espreafico"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013510.g006", "stats"=>{"downloads"=>4, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Structural_organization_phylogenetic_conservation_and_predicted_products_for_RMEL3_Hs_559350_/494136", "title"=>"Structural organization, phylogenetic conservation, and predicted products for <i>RMEL3</i> (Hs.559350).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-10-20 01:08:56"}
  • {"files"=>["https://ndownloader.figshare.com/files/823035"], "description"=>"<p>Relative expression was calculated according to 2<sup>−ΔΔCT</sup> method, using TBP (Tata-box binding protein) as endogenous control and the sample displaying the lowest normalized Ct as reference. The tissue panel included normal melanocytes (NM), melanoma cell lines (melanoma), including those harboring the activating BRAF V600E mutation (*), wild type BRAF (not marked), or with mutation status not determined (ND); and various cell lines and tissues of non-melanocytic origin (non-melanoma), including primary skin fibroblasts, HeLa, HL-60, Jurkat cells, peripheral blood mononuclear cells (PBMC), and necropsy samples from spleen, brain, esophagus, liver, intestine, skeletal muscle, kidney, normal bladder (NB), bladder tumor (BT), normal prostate (NP), prostate tumor (PT), normal glia (NG), gliobastoma (GBM).</p>", "links"=>[], "tags"=>["Real-time", "rt-pcr"], "article_id"=>493395, "categories"=>["Infectious Diseases", "Molecular Biology", "Genetics", "Cancer"], "users"=>["Josane F. Sousa", "Raul Torrieri", "Rodrigo R. Silva", "Cristiano G. Pereira", "Valeria Valente", "Erico Torrieri", "Kamila C. Peronni", "Waleska Martins", "Nair Muto", "Guilherme Francisco", "Carla Abdo Brohem", "Carlos G. Carlotti Jr.", "Silvya S. Maria-Engler", "Roger Chammas", "Enilza M. Espreafico"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013510.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Validation_by_real_time_RT_PCR_of_the_melanoma_melanocyte_restricted_expression_of_RMEL1_2_and_3_/493395", "title"=>"Validation by real-time RT-PCR of the melanoma/melanocyte-restricted expression of <i>RMEL1, 2</i> and <i>3</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-10-20 00:56:35"}
  • {"files"=>["https://ndownloader.figshare.com/files/823315"], "description"=>"<p>Patients were divided into two groups according to expression levels, classified as lower or equal and higher than the maximal detected in nevi, for <i>RMEL1</i>, and as detected (D) and non-detected (ND), for <i>RMEL2</i> and <i>RMEL3</i>. The Kaplan-Meier survival curves were calculated using the SPSS Statistics version 18.0 from SPSS (IBM Company).</p>", "links"=>[], "tags"=>["estimates", "cumulative", "melanoma", "patients"], "article_id"=>493668, "categories"=>["Infectious Diseases", "Molecular Biology", "Genetics", "Cancer"], "users"=>["Josane F. Sousa", "Raul Torrieri", "Rodrigo R. Silva", "Cristiano G. Pereira", "Valeria Valente", "Erico Torrieri", "Kamila C. Peronni", "Waleska Martins", "Nair Muto", "Guilherme Francisco", "Carla Abdo Brohem", "Carlos G. Carlotti Jr.", "Silvya S. Maria-Engler", "Roger Chammas", "Enilza M. Espreafico"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0013510.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kaplan_Meier_estimates_of_cumulative_survival_for_melanoma_patients_according_to_the_expression_of_RMEL1_A_RMEL2_B_and_RMEL3_C_/493668", "title"=>"Kaplan-Meier estimates of cumulative survival for melanoma patients according to the expression of <i>RMEL1</i> (A), <i>RMEL2</i> (B) and <i>RMEL3</i> (C).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-10-20 01:01:08"}
  • {"files"=>["https://ndownloader.figshare.com/files/410320", "https://ndownloader.figshare.com/files/410325", "https://ndownloader.figshare.com/files/410332", "https://ndownloader.figshare.com/files/410337", "https://ndownloader.figshare.com/files/410344", "https://ndownloader.figshare.com/files/410352", "https://ndownloader.figshare.com/files/410357", "https://ndownloader.figshare.com/files/410364"], "description"=>"<div><p>Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the <em>in silico</em> detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma.</p></div>", "links"=>[], "tags"=>["primate-specific", "rmel", "restricted", "assessed", "mining"], "article_id"=>141042, "categories"=>["Cancer", "Molecular Biology", "Genetics"], "users"=>["Josane F. Sousa", "Raul Torrieri", "Rodrigo R. Silva", "Cristiano G. Pereira", "Valeria Valente", "Erico Torrieri", "Kamila C. Peronni", "Waleska Martins", "Nair Muto", "Guilherme Francisco", "Carla Abdo Brohem", "Carlos G. Carlotti Jr.", "Silvya S. Maria-Engler", "Roger Chammas", "Enilza M. Espreafico"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0013510.s001", "https://dx.doi.org/10.1371/journal.pone.0013510.s002", "https://dx.doi.org/10.1371/journal.pone.0013510.s003", "https://dx.doi.org/10.1371/journal.pone.0013510.s004", "https://dx.doi.org/10.1371/journal.pone.0013510.s005", "https://dx.doi.org/10.1371/journal.pone.0013510.s006", "https://dx.doi.org/10.1371/journal.pone.0013510.s007", "https://dx.doi.org/10.1371/journal.pone.0013510.s008"], "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Novel_Primate_Specific_Genes_RMEL_1_2_and_3_with_Highly_Restricted_Expression_in_Melanoma_Assessed_by_New_Data_Mining_Tool/141042", "title"=>"Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-10-20 00:17:22"}

PMC Usage Stats | Further Information

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