Cyclooxygenase-2 Is a Target of MicroRNA-16 in Human Hepatoma Cells
Publication Date
November 30, 2012
Journal
PLOS ONE
Authors
Noelia Agra Andrieu, Omar Motiño, Rafael Mayoral, Cristina Llorente Izquierdo, et al
Volume
7
Issue
11
Pages
e50935
DOI
https://dx.plos.org/10.1371/journal.pone.0050935
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0050935
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23226427
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511388
Europe PMC
http://europepmc.org/abstract/MED/23226427
Web of Science
000312376100238
Scopus
84870609842
Mendeley
http://www.mendeley.com/research/cyclooxygenase2-target-microrna16-human-hepatoma-cells
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Mendeley | Further Information

{"title"=>"Cyclooxygenase-2 Is a Target of MicroRNA-16 in Human Hepatoma Cells", "type"=>"journal", "authors"=>[{"first_name"=>"Noelia", "last_name"=>"Agra Andrieu", "scopus_author_id"=>"55511835200"}, {"first_name"=>"Omar", "last_name"=>"Motiño", "scopus_author_id"=>"55321968400"}, {"first_name"=>"Rafael", "last_name"=>"Mayoral", "scopus_author_id"=>"35781976600"}, {"first_name"=>"Cristina", "last_name"=>"Llorente Izquierdo", "scopus_author_id"=>"35782100800"}, {"first_name"=>"Ana", "last_name"=>"Fernández-Alvarez", "scopus_author_id"=>"23027693100"}, {"first_name"=>"Lisardo", "last_name"=>"Boscá", "scopus_author_id"=>"35514045400"}, {"first_name"=>"Marta", "last_name"=>"Casado", "scopus_author_id"=>"7103101615"}, {"first_name"=>"Paloma", "last_name"=>"Martín-Sanz", "scopus_author_id"=>"57196054763"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"doi"=>"10.1371/journal.pone.0050935", "issn"=>"19326203", "sgr"=>"84870609842", "scopus"=>"2-s2.0-84870609842", "pui"=>"366207405", "pmid"=>"23226427", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)"}, "id"=>"0e462db9-eaa7-3b60-9867-1b0b1d09cbbb", "abstract"=>"Cyclooxygenase-2 (COX-2) expression has been detected in human hepatoma cell lines and in human hepatocellular carcinoma (HCC); however, the contribution of COX-2 to the development of HCC remains controversial. COX-2 expression is higher in the non-tumoral tissue and inversely correlates with the differentiation grade of the tumor. COX-2 expression depends on the interplay between different cellular pathways involving both transcriptional and post-transcriptional regulation. The aim of this work was to assess whether COX-2 could be regulated by microRNAs in human hepatoma cell lines and in human HCC specimens since these molecules contribute to the regulation of genes implicated in cell growth and differentiation. Our results show that miR-16 silences COX-2 expression in hepatoma cells by two mechanisms: a) by binding directly to the microRNA response element (MRE) in the COX-2 3'-UTR promoting translational suppression of COX-2 mRNA; b) by decreasing the levels of the RNA-binding protein Human Antigen R (HuR). Furthermore, ectopic expression of miR-16 inhibits cell proliferation, promotes cell apoptosis and suppresses the ability of hepatoma cells to develop tumors in nude mice, partially through targeting COX-2. Moreover a reduced miR-16 expression tends to correlate to high levels of COX-2 protein in liver from patients affected by HCC. Our data show an important role for miR-16 as a post-transcriptional regulator of COX-2 in HCC and suggest the potential therapeutic application of miR-16 in those HCC with a high COX-2 expression.", "link"=>"http://www.mendeley.com/research/cyclooxygenase2-target-microrna16-human-hepatoma-cells", "reader_count"=>23, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>1, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>13, "Neuroscience"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Business, Management and Accounting"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Neuroscience"=>{"Neuroscience"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"France"=>1, "Chile"=>1}, "group_count"=>2}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/534025"], "description"=>"<p>Hep3B cells were transfected with 50 nM miR-16 or miR-NC, or 30 nM siCOX-2. 5 µg/ml actinomycin-D (Act D) or 10 µg/ml cycloheximide (CHX) were added after transfection. (<b>A–B</b>) COX-2 protein was analyzed by Western blot at different time after actinomycin-D treatment. Corresponding densitometry analysis is shown and the relative expression of each sample is related to sample at 0 h as 1. (<b>C</b>) mRNA COX-2 levels were analyzed by real time PCR. COX-2 mRNA amounts were calculated as relative expression and normalized to the expression of 36b4 mRNA. Values represent fold change relative to sample at 0 h. (<b>D–E</b>) COX-2 protein levels were analyzed by Western blot in the presence or absence of cycloheximide. Corresponding densitometric analysis is shown and the relative expression of each sample is related to the value at 0 h as 1. <b>F)</b> Hep3B cells were transfected with 50 nM miR-16, miR-16 inhibitor (In-miR-16) or lipofectamine and permeabilized with digitonine to obtain soluble and pellet fractions enriched in PB as described in Methods. RNA was isolated from each fraction with Trizol reagent, reverse transcriptased, and PCR amplified with COX-2, Xrn1 and actin primers. Input, RNA extracted from cells prior to fractionation. PCR products were visualized by electrophoresis in SYBR Safe DNA gel stain agarose gels. <b>G)</b> The presence of COX-2 mRNA in soluble and PB fractions was assessed and fold differences were plotted. Data are reported as means±SD of three independent experiments. **p<0.01 and *p<0.05 vs. the value of sample at 0 h.</p>", "links"=>[], "tags"=>["mir-16", "cox-2", "mrna"], "article_id"=>204513, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050935.g004", "stats"=>{"downloads"=>2, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_miR_16_on_COX_2_mRNA_and_protein_stability_/204513", "title"=>"Effect of miR-16 on COX-2 mRNA and protein stability.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 01:15:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/533538"], "description"=>"<p>Cells were plated in 100-mm dishes and grown to 60–70% confluence in culture medium supplemented with 10% FBS. (<b>A</b>) Total cellular extracts were prepared from HCC cells and protein (30–50 µg/lane) was analyzed by Western blot. A representative Western blot showing COX-2 protein. The expression of target protein was normalized to that of α-tubulin. Densitometric analysis of COX-2 expression (black bars) is referring to HH as 1 and expressed as relative expression (RE). Total RNA was prepared from HCC cell lines and COX-2 mRNA was analyzed by real-time PCR. COX-2 mRNA amounts (white bars), normalized to the expression of 36b4 mRNA, and miR-16 expression (grey bars), normalized against U6 RNA levels, were calculated. Values represent fold change relative to human hepatocytes (HH) as 1. Data are reported as means±SD of three independent experiments. **<i>p<0.01</i> and <i>*p< 0.05 vs</i>. the HH. (<b>B</b>) The inverse correlation between COX-2 protein/mRNA ratio and miR-16 expression in HCC cells is graphically depicted. The coefficient of determination (R<sup>2</sup>) was calculated.</p>", "links"=>[], "tags"=>["cox-2", "correlate", "inversely", "hcc"], "article_id"=>204027, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050935.g001", "stats"=>{"downloads"=>1, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_16_and_COX_2_correlate_inversely_in_HCC_cell_lines_/204027", "title"=>"miR-16 and COX-2 correlate inversely in HCC cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 01:07:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/533857"], "description"=>"<p>(<b>A</b>) WRL68 cell extracts (500 µg per lane) were immunoprecipitated with Ago-2 or IgG antibodies. Bound RNA was harvested with TRIzol reagent, reverse transcriptased, and PCR amplified with COX-2 primers. PCR products were visualized by electrophoresis in SYBR Safe DNA gel stain agarose gels. The presence of COX-2 mRNA in WRL68 cell transfected with miR-16 or Lipofectamine after Ago2 immunoprecipitation was assessed, and fold differences were plotted. Input, total mRNA in cell extract; and control, bound mRNA after immunoprecipitation with IgG antiboby. (<b>B</b>) Scheme of pGL3-empty, pGL3-seed and pGL3-mut reporter vectors. In pGL3-seed, the putative binding site of miR-16 on COX-2 mRNA 3′-UTR region (as detected by RNAhybrid software) was introduced downstream luciferase gene. In pGL3-mut this region was mutated in order to avoid the binding between miR-16 and Luc mRNA. (<b>C–D</b>) A luciferase assay was carried out on HuH-7 and HepG2 cell lines using pGL3-seed and pGL3-mut reporter vectors. Firefly luciferase activity was evaluated 48 h after co-transfection with pGL3-empty/seed/mut (750 ng), miR-16 (50 nM), In-miR-16 (50 nM) and miR-NC (50 nM) as indicated. Data were normalized against renilla luciferase activity (all samples were co-transfected with 50 ng pRL vector and refer to the positive control, pGL3 empty vector). Data are reported as means±SD of three independent experiments. <i>*p< 0.05 vs</i>. the pGL3-empty condition and # <i>p< 0.05 vs</i>. the miR-16 transfection condition.</p>", "links"=>[], "tags"=>["binds", "cox-2", "mrna", "inhibits"], "article_id"=>204342, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050935.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_16_binds_COX_2_mRNA_and_inhibits_its_translation_/204342", "title"=>"miR-16 binds COX-2 mRNA and inhibits its translation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 01:12:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/534324"], "description"=>"<p>Hep3B cells were transfected with 50 nM miR-16 or In-miR-16 in the presence or absence of 5 µM PGE<sub>2</sub> (<b>A</b>) Apoptosis was measured with Annexin V-FITC Apoptosis Detection Kit (<b>B</b>) Western blot analysis of caspase-3. Results are the means ± SD of three different experiments. <i>*p< 0.05 vs</i>. the corresponding control cells <i><sup>#</sup> p< 0.05 vs.</i> miR-16 condition.</p>", "links"=>[], "tags"=>["cox-2", "mir-16", "increases", "apoptosis", "hcc"], "article_id"=>204806, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050935.g006", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Downregulation_of_COX_2_by_miR_16_increases_apoptosis_in_HCC_cells_/204806", "title"=>"Downregulation of COX-2 by miR-16 increases apoptosis in HCC cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 01:20:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/534144"], "description"=>"<p>WRL68 cell extracts (500 µg per lane) were immunoprecipitated with HuR or IgG antibodies. Bound RNA was harvested with TRIzol reagent, reverse transcriptased, and PCR amplified with COX-2 (<b>A</b>) or miR-16 primers (<b>B</b>). PCR products were visualized by electrophoresis in SYBR Safe DNA gel stain agarose gels. The abundance of the transcripts present in WRL68 cells after HuR immunoprecipitation was assessed, and fold differences were plotted. Input, total mRNA in cell extract; unbound, unbound mRNA after immunoprecipitation with HuR antibody; bound, bound mRNA after immunoprecipitation with HuR antibody; and control, bound mRNA after immunoprecipitation with IgG antiboby. (<b>C–D</b>) WRL68 and Hep3B cell lines were transfected with miR-16 or In-miR-16 (50 nM). COX-2 and HuR protein levels were analyzed by Western Blot. (<b>E–F</b>) WRL68 and Hep3B cell lines were cotransfected with miR-16 (50 nM) and pcDNA3-HuR-GFP expression vector (4 µg). COX-2 and HuR protein levels were analyzed by Western Blot. Data are reported as means±SD of three independent experiments. <i>*p< 0.05 vs</i>. the control condition and # <i>p< 0.05 vs</i>. the miR-16 transfection condition.</p>", "links"=>[], "tags"=>["antagonizes", "downregulation", "cox-2", "caused", "mir-16", "hepatoma"], "article_id"=>204629, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050935.g005", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HuR_antagonizes_the_downregulation_of_COX_2_expression_caused_by_miR_16_in_hepatoma_cell_lines_/204629", "title"=>"HuR antagonizes the downregulation of COX-2 expression caused by miR-16 in hepatoma cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 01:17:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/534527"], "description"=>"<p>The miRNAs (miR-16, miR-26b, miR-101, miR-199a, miR-122 and miR-21) were selected by using miRWalk computational analysis as described in Methods. The expression profile was analyzed in HCC cell lines using real-time PCR, normalized against U6 RNA levels and refers to human hepatocytes (HH) as 1. COX-2 protein/mRNA ratio was compared to miRNAs expression in HCC cells and the coefficient of determination (R<sup>2</sup>) was calculated.</p>", "links"=>[], "tags"=>["mirnas", "evaluated", "hcc"], "article_id"=>205014, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050935.t001", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_selected_miRNAs_is_evaluated_in_HCC_cell_lines_/205014", "title"=>"Expression of selected miRNAs is evaluated in HCC cell lines.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-11-30 01:23:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/534438"], "description"=>"<p>(<b>A</b>) Hep3B cells were transfected with 50 nM miR-16 or In-miR-16. The effect on cell proliferation was determined by MTT assay at 48 h after transfection. <i>*p< 0.05 </i><i>vs</i>. the control and # <i>p< 0.05 </i><i>vs</i>. the miR-16 transfection condition. (<b>B</b>) Tumor growth curves measured after subcutaneous injection of WRL68 cells transiently transfected with miR-16, miR-NC or miR-16 with a hCOX-2 expression vector lacking 3′ UTR (miR-16+COX-2). Tumor volume (V) was monitored by measuring the length (L) and width (W) with calipers and calculated with the formula (L×W<sup>2</sup>)×0.5. Tumor growth was measured every 2–3 days. <i>*p< 0.05 </i><i>vs</i>. the miR-NC and # p<0.05 <i>vs.</i> miR-16 (<b>C</b>) Tumor weight and a representative picture of the tumors. At 21 days after injection, mice were killed and tumors were weighed after necropsy. <i>*p< 0.05 </i><i>vs</i>. the miR-NC or # <i>vs.</i> the miR-16+ COX-2 condition. (<b>D–E</b>) miR-16 and human COX-2 expression in tumors using real-time PCR normalized against U6 RNA levels and refers to miR-NC as 1 or 36b4 mRNA, respectively. <i>*p< 0.05 </i><i>vs</i>. the miR-NC Data are reported as means±SD of three independent experiments or five animals per condition.</p>", "links"=>[], "tags"=>["suppresses", "hepatoma", "cells", "vitro", "tumorigenicity"], "article_id"=>204921, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050935.g007", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_16_suppresses_growth_of_hepatoma_cells_in_vitro_and_tumorigenicity_in_vivo_/204921", "title"=>"miR-16 suppresses growth of hepatoma cells in vitro and tumorigenicity <i>in vivo.</i>", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 01:22:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/287977", "https://ndownloader.figshare.com/files/288021", "https://ndownloader.figshare.com/files/288077"], "description"=>"<div><p>Cyclooxygenase-2 (COX-2) expression has been detected in human hepatoma cell lines and in human hepatocellular carcinoma (HCC); however, the contribution of COX-2 to the development of HCC remains controversial. COX-2 expression is higher in the non-tumoral tissue and inversely correlates with the differentiation grade of the tumor. COX-2 expression depends on the interplay between different cellular pathways involving both transcriptional and post-transcriptional regulation. The aim of this work was to assess whether COX-2 could be regulated by microRNAs in human hepatoma cell lines and in human HCC specimens since these molecules contribute to the regulation of genes implicated in cell growth and differentiation. Our results show that miR-16 silences COX-2 expression in hepatoma cells by two mechanisms: a) by binding directly to the microRNA response element (MRE) in the COX-2 3′-UTR promoting translational suppression of COX-2 mRNA; b) by decreasing the levels of the RNA-binding protein Human Antigen R (HuR). Furthermore, ectopic expression of miR-16 inhibits cell proliferation, promotes cell apoptosis and suppresses the ability of hepatoma cells to develop tumors in nude mice, partially through targeting COX-2. Moreover a reduced miR-16 expression tends to correlate to high levels of COX-2 protein in liver from patients affected by HCC. Our data show an important role for miR-16 as a post-transcriptional regulator of COX-2 in HCC and suggest the potential therapeutic application of miR-16 in those HCC with a high COX-2 expression.</p> </div>", "links"=>[], "tags"=>["cyclooxygenase-2", "microrna-16", "hepatoma", "cells"], "article_id"=>116731, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0050935.s001", "https://dx.doi.org/10.1371/journal.pone.0050935.s002", "https://dx.doi.org/10.1371/journal.pone.0050935.s003"], "stats"=>{"downloads"=>4, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Cyclooxygenase_2_Is_a_Target_of_MicroRNA_16_in_Human_Hepatoma_Cells__/116731", "title"=>"Cyclooxygenase-2 Is a Target of MicroRNA-16 in Human Hepatoma Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-11-30 01:52:11"}
  • {"files"=>["https://ndownloader.figshare.com/files/533660"], "description"=>"<p>WRL68 and Hep3B cells were transfected with: 30 nM siRNA anti-COX2 (siCOX-2) or 50 nM of miR-16, miR-16 inhibitor (In-miR-16), miR negative control (miR-NC) or miR negative control inhibitor (In-miR-NC). (<b>A–B</b>) COX-2 protein was analyzed by Western blot 48 h after transfection and normalized against α-tubulin protein. COX-2 mRNA and miR-16 expression were analyzed by real-time PCR. COX-2 mRNA and miR-16 expression were normalized against 36b4 mRNA and U6 RNA levels, respectively. Relative expression of each sample refers to control as 1 (cells transfected only with lipofectamine). (<b>C–D</b>) PGE<sub>2</sub> concentration was determined by enzyme immunoassay in the supernatant of the cells. Data are reported as means±SD of four independent experiments. <i>*p< 0.05 vs</i>. the control condition and # <i>p< 0.05 vs</i>. the miR-16 transfection condition.</p>", "links"=>[], "tags"=>["regulates", "cox-2", "hcc"], "article_id"=>204149, "categories"=>["Molecular Biology", "Chemistry", "Biophysics", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Noelia Agra Andrieu", "Omar Motiño", "Rafael Mayoral", "Cristina Llorente Izquierdo", "Ana Fernández-Alvarez", "Lisardo Boscá", "Marta Casado", "Paloma Martín-Sanz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0050935.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_miR_16_regulates_COX_2_expression_in_HCC_cell_lines_/204149", "title"=>"miR-16 regulates COX-2 expression in HCC cell lines.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-30 01:09:09"}

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Relative Metric

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