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{"title"=>"Overexpression of piRNA pathway genes in epithelial ovarian cancer", "type"=>"journal", "authors"=>[{"first_name"=>"Shu Ly", "last_name"=>"Lim", "scopus_author_id"=>"35760373300"}, {"first_name"=>"Carmela", "last_name"=>"Ricciardelli", "scopus_author_id"=>"6602995373"}, {"first_name"=>"Martin K.", "last_name"=>"Oehler", "scopus_author_id"=>"56087140400"}, {"first_name"=>"Izza M D", "last_name"=>"De Arao Tan", "scopus_author_id"=>"55621335100"}, {"first_name"=>"Darryl", "last_name"=>"Russell", "scopus_author_id"=>"7403670173"}, {"first_name"=>"Frank", "last_name"=>"Grützner", "scopus_author_id"=>"55628578399"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84903316848", "pui"=>"373394676", "doi"=>"10.1371/journal.pone.0099687", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "sgr"=>"84903316848", "pmid"=>"24932571"}, "id"=>"c1c6a86d-e2a0-3da4-9442-a7a40e5043cc", "abstract"=>"The importance of the Piwi-interacting RNA (piRNA) pathway for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control raises possible roles of this pathway in cancer. Indeed aberrant expression of human PIWI orthologs and Maelstrom has been observed in various cancers. In this study we explored the expression and function of piRNA pathway genes in human ovarian cancer, based on our recent work, which showed widespread expression of piRNA pathway genes in the mammalian. Our work shows that PIWIL1 and MAEL expression is significantly increased in malignant EOC (n = 25) compared to benign tumor tissues (n = 19) and normal ovarian tissue (n = 8). The expression of PIWIL3 is lower in malignant and benign tissues when compared to normal ovary. Sequencing of PIWIL1 transcript revealed that in many tumors deletion of exon 17 leads to the introduction of a premature stop codon in the PIWI domain, likely due to a splicing error. In situ hybridization on tumor sections revealed that L1, PIWIL1, 2 and MAEL are specifically expressed in epithelial cells (cancerous cells) of EOC. Furthermore, PIWIL2 and MAEL are co-expressed in the stromal cells adjacent to tumor cells. Since PIWIL1 and MAEL are up regulated in malignant EOC and expressed in the epithelial cells, we investigated if these two genes affect invasiveness of ovarian cancer cell lines that do not normally express these genes. PIWIL1 and MAEL were transiently over expressed in the ovarian cancer cell line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly both PIWIL1 and MAEL over expression decreased the invasiveness of SKOV3 cells. Our findings support a growing body of evidence that shows that genes in this pathway are upregulated in cancer. In ovarian cancer we show for the first time that Piwil1 transcript may often be abnormal result in non functional product. In contrast to what has been observed in other cell types, we found that PIWIL1 and MAEL have a repressive effect on cell invasiveness.", "link"=>"http://www.mendeley.com/research/overexpression-pirna-pathway-genes-epithelial-ovarian-cancer", "reader_count"=>35, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>14, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>14, "Student > Ph. D. Student"=>13, "Student > Postgraduate"=>1, "Student > Master"=>3, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>9, "Agricultural and Biological Sciences"=>23, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>23}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>9}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United States"=>2, "Egypt"=>1}, "group_count"=>0}

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• http://doi.org/10.1002/ijc.30388
• http://doi.org/10.1002/mc.22285
• http://doi.org/10.1007/s00125-017-4368-2
• http://doi.org/10.1007/s12013-015-0651-3
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• http://doi.org/10.1186/s13048-018-0475-z

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• {"files"=>["https://ndownloader.figshare.com/files/1536288", "https://ndownloader.figshare.com/files/1536289", "https://ndownloader.figshare.com/files/1536290", "https://ndownloader.figshare.com/files/1536291", "https://ndownloader.figshare.com/files/1536292", "https://ndownloader.figshare.com/files/1536293", "https://ndownloader.figshare.com/files/1536294"], "description"=>"<div><p>The importance of the Piwi-interacting RNA (piRNA) pathway for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control raises possible roles of this pathway in cancer. Indeed aberrant expression of human PIWI orthologs and <i>Maelstrom</i> has been observed in various cancers. In this study we explored the expression and function of piRNA pathway genes in human ovarian cancer, based on our recent work, which showed widespread expression of piRNA pathway genes in the mammalian. Our work shows that <i>PIWIL1</i> and <i>MAEL</i> expression is significantly increased in malignant EOC (n = 25) compared to benign tumor tissues (n = 19) and normal ovarian tissue (n = 8). The expression of <i>PIWIL3</i> is lower in malignant and benign tissues when compared to normal ovary. Sequencing of <i>PIWIL1</i> transcript revealed that in many tumors deletion of exon 17 leads to the introduction of a premature stop codon in the PIWI domain, likely due to a splicing error. <i>In situ</i> hybridization on tumor sections revealed that <i>L1</i>, <i>PIWIL1</i>, <i>2</i> and <i>MAEL</i> are specifically expressed in epithelial cells (cancerous cells) of EOC. Furthermore, <i>PIWIL2</i> and <i>MAEL</i> are co-expressed in the stromal cells adjacent to tumor cells. Since <i>PIWIL1</i> and <i>MAEL</i> are up regulated in malignant EOC and expressed in the epithelial cells, we investigated if these two genes affect invasiveness of ovarian cancer cell lines that do not normally express these genes. <i>PIWIL1</i> and <i>MAEL</i> were transiently over expressed in the ovarian cancer cell line SKOV3, followed by real-time measurements of cell invasiveness. Surprisingly both <i>PIWIL1</i> and <i>MAEL</i> over expression decreased the invasiveness of SKOV3 cells. Our findings support a growing body of evidence that shows that genes in this pathway are upregulated in cancer. In ovarian cancer we show for the first time that <i>Piwil1</i> transcript may often be abnormal result in non functional product. In contrast to what has been observed in other cell types, we found that <i>PIWIL1</i> and <i>MAEL</i> have a repressive effect on cell invasiveness.</p></div>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "pirna", "pathway", "genes", "epithelial", "ovarian"], "article_id"=>1058555, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0099687.s001", "https://dx.doi.org/10.1371/journal.pone.0099687.s002", "https://dx.doi.org/10.1371/journal.pone.0099687.s003", "https://dx.doi.org/10.1371/journal.pone.0099687.s004", "https://dx.doi.org/10.1371/journal.pone.0099687.s005", "https://dx.doi.org/10.1371/journal.pone.0099687.s006", "https://dx.doi.org/10.1371/journal.pone.0099687.s007"], "stats"=>{"downloads"=>8, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Overexpression_of_piRNA_Pathway_Genes_in_Epithelial_Ovarian_Cancer_/1058555", "title"=>"Overexpression of piRNA Pathway Genes in Epithelial Ovarian Cancer", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-06-16 03:13:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1536270"], "description"=>"<p>RT-PCR analyses of <i>PIWIL1-4</i> and <i>MAEL</i> expression in (A) malignant EOC, benign ovarian cancers (B) normal ovaries and (C) ovarian cancer cell lines. This is a representation of 4 out of 25 malignant EOC and 19 benign ovarian cancer tissues. Increased expression of <i>PIWIL1, 2, 4</i> and <i>MAEL</i>, but not <i>PIWIL3</i>, are found in malignant cancers compared to benign tumors. All normal ovaries show <i>PIWIL2</i> and <i>PIWIL4</i> expression but only some have <i>PIWIL1, 3</i> and <i>MAEL</i> expression. No endogenous <i>PIWIL1, 2, 4</i> and <i>MAEL</i> expression is detected in OVCAR3 and SKOV3 cells. Ova* indicates tissue from a 20-year old pre-menopausal ovary while other ovaries are from individuals aged 44–76 years old.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "pathway", "ovaries", "ovarian"], "article_id"=>1058537, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099687.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_piRNA_pathway_gene_expression_in_human_normal_ovaries_and_ovarian_cancers_/1058537", "title"=>"piRNA pathway gene expression in human normal ovaries and ovarian cancers.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-16 03:13:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1536282"], "description"=>"<p>(A) <i>PIWIL1</i> expression in control tissues (human testis, normal ovary (ov) 1, 2) and EOC tissue SC1 and 2. In the positive control, a 500 bp band was amplified, but in malignant SC1, two bands were obtained. (B) cDNA multiple alignment (partial) showing that most of the clones have a deletion of exon 17 (ΔΔ3) and 3 clones have partial splicing of intron 15 and 16 (). PIWIL1_ccds: published cDNA of <i>PIWIL1</i> (CCDS9268); Testis C1: testis transcript clone 1; B1–3, B6, B9–B14, C6, C8, C9, C10–C15, D1–D10: clones with <i>PIWIL1</i> transcripts.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "transcript", "variants"], "article_id"=>1058549, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099687.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_PIWIL1_transcript_variants_in_EOC_/1058549", "title"=>"<i>PIWIL1</i> transcript variants in EOC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-16 03:13:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1536275"], "description"=>"<p><i>In situ</i> analysis of (A, A’, E) <i>L1</i>, (B, B’, F) <i>PIWIL1</i>, (C, C’, G) <i>MAEL</i>, (D, D’, H) <i>PIWIL2</i> in two malignant EOC (A-D from SC3 while E-H from SC2). (A’-D’) Amplification images of A-D respectively. Strong expression of piRNA pathway genes and <i>L1</i> was found in the squamous-to-cuboidal like epithelial cells of both malignant EOC except <i>PIWIL1</i> which only expressed in SC2 but not SC3. <i>L1</i> has patchy expression in some EOC such that some epithelial cells seem to have stronger <i>L1</i> expression compared to others. <i>MAEL</i> and <i>PIWIL2</i> but not <i>PIWIL1</i> are also expressed in the stromal cells in both EOC. (E’-H’) Negative controls with sense probe of <i>L1</i>, <i>PIWIL1</i>, <i>MAEL</i> and <i>PIWIL2</i> respectively. Ep  =  epithelial cells; S  =  stromal cells. Scale bar  =  50µm.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "epithelial", "cells", "malignant"], "article_id"=>1058542, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099687.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_L1_PIWIL1_MAEL_and_PIWIL2_are_expressed_in_the_epithelial_cells_of_malignant_EOC_/1058542", "title"=>"<i>L1</i>, <i>PIWIL1</i>, <i>MAEL</i> and <i>PIWIL2</i> are expressed in the epithelial cells of malignant EOC.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-16 03:13:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1536286"], "description"=>"<p>Spearman's correlation test; M  =  malignant; B  =  benign; N  =  normal; negative value  =  negative correlation; positive value  =  positive correlation; P <0.05 and * indicates the correlation between the age of patients and piRNA pathway gene expression is significant. The R-value closer to ± 1 indicates the stronger correlation.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "patients", "pirna", "pathway"], "article_id"=>1058553, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099687.t002", "stats"=>{"downloads"=>5, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Correlation_between_age_of_patients_and_piRNA_pathway_gene_expression_/1058553", "title"=>"Correlation between age of patients and piRNA pathway gene expression.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-16 03:13:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1536271"], "description"=>"<p>Semi-quantitative RT-PCR analysis of mRNA expression (relative to <i>ACTB</i>) of (A) <i>PIWIL1</i>, (B) <i>MAEL</i>, (C) <i>PIWIL2</i>, (D) <i>PIWIL4</i> and (E) <i>PIWIL3</i>. (F) P-value of each comparison group. Malignant EOC (n = 25), benign ovarian cancer tissues (n = 19) and normal ovaries (n = 8). Kruskal-Wallis Test was performed to compare the gene expression level between two groups. Filled dot indicates mean of each group. * indicates 0.001</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "pirna", "pathway", "genes", "malignant", "benign", "ovarian", "cancer", "tissues"], "article_id"=>1058538, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099687.g002", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Box_plot_representing_the_expression_of_piRNA_pathway_genes_in_malignant_EOC_benign_ovarian_cancer_tissues_and_normal_ovaries_/1058538", "title"=>"Box plot representing the expression of piRNA pathway genes in malignant EOC, benign ovarian cancer tissues and normal ovaries.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-16 03:13:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1536284"], "description"=>"<p>Age and cancer stage of EOC, benign tumors and normal ovaries.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "cancer", "benign", "tumors"], "article_id"=>1058551, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099687.t001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Age_and_cancer_stage_of_EOC_benign_tumors_and_normal_ovaries_/1058551", "title"=>"Age and cancer stage of EOC, benign tumors and normal ovaries.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-16 03:13:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1536285"], "description"=>"<p>“-“: undetectable expression.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "trends", "pirna", "pathway", "genes", "eoc"], "article_id"=>1058552, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099687.t003", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_trends_of_piRNA_pathway_genes_and_L1_in_the_EOC_after_in_situ_hybridisation_/1058552", "title"=>"Expression trends of piRNA pathway genes and <i>L1</i> in the EOC after <i>in situ</i> hybridisation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-06-16 03:13:30"}
• {"files"=>["https://ndownloader.figshare.com/files/1536283"], "description"=>"<p><i>PIWIL1</i> and <i>MAEL</i> transfected cells have lower invasiveness compared to untransfected cells and <i>Ev</i> transfected cells. In each experiment, each group was performed in triplicate and this experiment was repeated three times. This is a combined data plot of three independent experiments for all groups. Error bars represent standard deviation. <i>WT</i> indicates untransfected SKOV3 cells; empty vector (Ev), <i>MAEL</i> and <i>PIWIL1</i> indicate cells transfected with <i>MAEL</i> or <i>PIWIL1</i> vectors. <i>None</i> indicates well without cells.</p>", "links"=>[], "tags"=>["genetics", "gene expression", "DNA transcription", "Cancer genetics", "Clinical genetics", "oncology", "Cancers and neoplasms", "Gynecological tumors", "Ovarian cancer", "Basic cancer research", "women's health", "assay", "transfected", "skov3"], "article_id"=>1058550, "categories"=>["Biological Sciences"], "users"=>["Shu Ly Lim", "Carmela Ricciardelli", "Martin K. Oehler", "Izza M. D. De Arao Tan", "Darryl Russell", "Frank Grützner"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0099687.g005", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Invasion_assay_of_MAEL_or_PIWIL1_transfected_SKOV3_cells_/1058550", "title"=>"Invasion assay of <i>MAEL</i> or <i>PIWIL1</i> transfected SKOV3 cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-06-16 03:13:30"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime