The Rescue of miR-148a Expression in Pancreatic Cancer: An Inappropriate Therapeutic Tool
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{"title"=>"The Rescue of miR-148a Expression in Pancreatic Cancer: An Inappropriate Therapeutic Tool", "type"=>"journal", "authors"=>[{"first_name"=>"Yannick", "last_name"=>"Delpu", "scopus_author_id"=>"36479905600"}, {"first_name"=>"Hubert", "last_name"=>"Lulka", "scopus_author_id"=>"8225561300"}, {"first_name"=>"Flavie", "last_name"=>"Sicard", "scopus_author_id"=>"8756622100"}, {"first_name"=>"Nathalie", "last_name"=>"Saint-Laurent", "scopus_author_id"=>"6602548143"}, {"first_name"=>"Frédéric", "last_name"=>"Lopez", "scopus_author_id"=>"7202047898"}, {"first_name"=>"Naïma", "last_name"=>"Hanoun", "scopus_author_id"=>"6701625227"}, {"first_name"=>"Louis", "last_name"=>"Buscail", "scopus_author_id"=>"7005859539"}, {"first_name"=>"Pierre", "last_name"=>"Cordelier", "scopus_author_id"=>"6602836331"}, {"first_name"=>"Jérôme", "last_name"=>"Torrisani", "scopus_author_id"=>"6507137334"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84873208217", "pui"=>"368246935", "doi"=>"10.1371/journal.pone.0055513", "pmid"=>"23383211", "scopus"=>"2-s2.0-84873208217", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)"}, "id"=>"ce90bab7-3ec3-302b-9967-0f0fa2f11d96", "abstract"=>"MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, in vivo data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both in vitro and in vivo thus suggesting a weak potential as a therapeutic tool.", "link"=>"http://www.mendeley.com/research/rescue-mir148a-expression-pancreatic-cancer-inappropriate-therapeutic-tool", "reader_count"=>14, "reader_count_by_academic_status"=>{"Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Other"=>1, "Student > Master"=>1, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Portugal"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/497313"], "description"=>"<p>(<b>A</b>) Capan-2, PANC-1, MIA PaCa-2 and BxPC-3 PDAC-derived cell lines and non-cancerous HPNE cell line were transiently transfected with miR-CT or miR-148a precursors. Four days after transfection, cell viability was assessed by colorimetric methods. For each cell line, the miR-148a-cell viability was compared to miR-CT cell viability (100%). The results are the mean of three independent experiments (±SEM) and are expressed as percentage of cell viability of control cells. (<b>B</b>), Cell cycle distribution was measured by propidium iodide staining followed by FACS analysis 72 hours after transfection of Capan-2 cells with miR-CT or miR-148a precursors.</p>", "links"=>[], "tags"=>["over-expression", "mir-148a", "pdac"], "article_id"=>167822, "categories"=>["Biochemistry", "Chemistry", "Cancer", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Yannick Delpu", "Hubert Lulka", "Flavie Sicard", "Nathalie Saint-Laurent", "Frédéric Lopez", "Naïma Hanoun", "Louis Buscail", "Pierre Cordelier", "Jérôme Torrisani"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055513.g001", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Transient_over_expression_of_miR_148a_in_PDAC_cell_lines_/167822", "title"=>"Transient over-expression of miR-148a in PDAC cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:10:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/497566"], "description"=>"<p>(<b>A</b>) <i>In vivo</i> monitoring of xenograft tumor progression: MIA PaCa-2 cells expressing miR-148a and secreted Gaussia luciferase (Gluc) were injected in the pancreas of SCID mice. Mice received normal water (untreated, n = 10) or water supplemented with doxycycline (doxycycline, n = 12) for miR-148a expression induction until sacrifice. Gluc levels were measured in mice serum. The results are the mean of Gluc activities (±SEM) and are expressed as Arbitrary Light Unit (A.L.U.). (<b>B</b>) Tumors were removed and weighted the day of surgery. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055513#s3\" target=\"_blank\">Results</a> are mean (±SEM) of tumor weight in the untreated group (n = 10) and the doxycycline treated group (n = 12) (<b>C</b>) <i>In vivo</i> monitoring of xenograft tumor progression: MIA PaCa-2 cells expressing secreted Gaussia luciferase were injected in the pancreas of SCID mice (n = 10). Fifteen days later, lentiviral vectors encoding miR-148a (miR-148a, n = 7) or GFP only (GFP, n = 3) were injected in the tumors (the arrow indicates the lentiviral particles injection). The amount of Gluc was measured in mice serum and compared to the Gluc amount measured the day of lentivector injection (Day 0). The results are the mean of the Gluc level ratio in each group (±SEM) and are expressed as arbitrary light unit ratio. (<b>D</b>) Tumors receiving miR-148 (miR-148a, n = 7) or GFP (GFP, n = 3) were removed 10 days after lentiviral injection and were weighted. The graph represents the comparison of tumor weight expressing miR-148a (n = 7) or GFP (n = 3). The results are the mean of tumor weight in each group (±SEM).</p>", "links"=>[], "tags"=>["orthotopic", "xenograft", "progression"], "article_id"=>168079, "categories"=>["Biochemistry", "Chemistry", "Cancer", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Yannick Delpu", "Hubert Lulka", "Flavie Sicard", "Nathalie Saint-Laurent", "Frédéric Lopez", "Naïma Hanoun", "Louis Buscail", "Pierre Cordelier", "Jérôme Torrisani"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055513.g004", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Murine_orthotopic_xenograft_and_tumor_progression_monitoring_/168079", "title"=>"Murine orthotopic xenograft and tumor progression monitoring.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:14:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/497419"], "description"=>"<p>MIA PaCa-2 cells were incubated with inducible lentiviral vectors encoding for scramble microRNA (miR-CT) or miR-148a (miR-148a). MIA PaCa-2 miR-CT or miR-148a proliferation rate was assessed in the presence or the absence of doxycycline in culture medium. For each condition, cell count was performed every 24 h and compared to the number of adherent cells at day 1. The results are the mean of three independent experiments (±SEM).</p>", "links"=>[], "tags"=>["mir-148a", "over-expression", "pdac"], "article_id"=>167934, "categories"=>["Biochemistry", "Chemistry", "Cancer", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Yannick Delpu", "Hubert Lulka", "Flavie Sicard", "Nathalie Saint-Laurent", "Frédéric Lopez", "Naïma Hanoun", "Louis Buscail", "Pierre Cordelier", "Jérôme Torrisani"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055513.g002", "stats"=>{"downloads"=>2, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_stable_miR_148a_over_expression_in_PDAC_cell_line_/167934", "title"=>"Effect of stable miR-148a over-expression in PDAC cell line.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:12:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/480960", "https://ndownloader.figshare.com/files/480963", "https://ndownloader.figshare.com/files/480965", "https://ndownloader.figshare.com/files/480966", "https://ndownloader.figshare.com/files/480967", "https://ndownloader.figshare.com/files/480970", "https://ndownloader.figshare.com/files/480971"], "description"=>"<div><p>MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, <em>in vivo</em> data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both <em>in vitro</em> and <em>in vivo</em> thus suggesting a weak potential as a therapeutic tool.</p> </div>", "links"=>[], "tags"=>["mir-148a", "pancreatic", "inappropriate", "therapeutic", "tool"], "article_id"=>155242, "categories"=>["Biochemistry", "Chemistry", "Cancer", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Yannick Delpu", "Hubert Lulka", "Flavie Sicard", "Nathalie Saint-Laurent", "Frédéric Lopez", "Naïma Hanoun", "Louis Buscail", "Pierre Cordelier", "Jérôme Torrisani"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0055513.s001", "https://dx.doi.org/10.1371/journal.pone.0055513.s002", "https://dx.doi.org/10.1371/journal.pone.0055513.s003", "https://dx.doi.org/10.1371/journal.pone.0055513.s004", "https://dx.doi.org/10.1371/journal.pone.0055513.s005", "https://dx.doi.org/10.1371/journal.pone.0055513.s006", "https://dx.doi.org/10.1371/journal.pone.0055513.s007"], "stats"=>{"downloads"=>0, "page_views"=>44, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/The_Rescue_of_miR_148a_Expression_in_Pancreatic_Cancer_An_Inappropriate_Therapeutic_Tool__/155242", "title"=>"The Rescue of miR-148a Expression in Pancreatic Cancer: An Inappropriate Therapeutic Tool", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-01-31 01:27:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/497485"], "description"=>"<p>(<b>A</b>) miR-148a endogenous expression level was measured by qRT-PCR in several PDAC cell lines and in hPDE and hPNE normal pancreatic cell lines. (<b>B</b>) Cell sensitivity to gemcitabine was measured after a 72 h-treatment in several PDAC cell lines and in normal hPNE pancreatic cells. Surviving cell fraction represents the number of treated cells during 72 h compared to the number of untreated cells (represented as 100%). The lethal concentration 50 (LC50) represents the dose of gemcitabine sufficient to obtain 50% of surviving cells compared to untreated cells. The results are the mean of three independent experiments (±SEM). (<b>C</b>) Cell sensitivity to gemcitabine was measured in MIA PaCa-2 cells stably over-expressing miR-148a (LV-TO-miR-148a) or a control miR (LV-TO-miR-CT) to gemcitabine in presence of doxycycline after a 72 h-treatment. Surviving cell fraction represents the number of treated cells during 72 h compared to the number of untreated cells (represented as 100%). The results are the mean of three independent experiments (±SEM).</p>", "links"=>[], "tags"=>["pdac", "lines", "over-expressing"], "article_id"=>168001, "categories"=>["Biochemistry", "Chemistry", "Cancer", "Molecular Biology", "Cell Biology", "Genetics"], "users"=>["Yannick Delpu", "Hubert Lulka", "Flavie Sicard", "Nathalie Saint-Laurent", "Frédéric Lopez", "Naïma Hanoun", "Louis Buscail", "Pierre Cordelier", "Jérôme Torrisani"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0055513.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Gemcitabine_sensitivity_of_PDAC_cell_lines_over_expressing_miR_148a_/168001", "title"=>"Gemcitabine sensitivity of PDAC cell lines over-expressing miR-148a.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-01-31 02:13:21"}

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Relative Metric

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