MiR-375 Is Epigenetically Downregulated by HPV-16 E6 Mediated DNMT1 Upregulation and Modulates EMT of Cervical Cancer Cells by Suppressing lncRNA MALAT1
Publication Date
September 22, 2016
Journal
PLOS ONE
Authors
Shikai Liu, Lili Song, Hairong Yao, Liang Zhang, et al
Volume
11
Issue
9
Pages
e0163460
DOI
https://dx.plos.org/10.1371/journal.pone.0163460
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0163460
Scopus
84992176867
Mendeley
http://www.mendeley.com/research/mir375-epigenetically-downregulated-hpv16-e6-mediated-dnmt1-upregulation-modulates-emt-cervical-canc
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Mendeley | Further Information

{"title"=>"MiR-375 is epigenetically downregulated by HPV-16 E6 mediated DNMT1 upregulation and modulates EMT of cervical cancer cells by suppressing IncRNA MALAT1", "type"=>"journal", "authors"=>[{"first_name"=>"Shikai", "last_name"=>"Liu", "scopus_author_id"=>"56306257500"}, {"first_name"=>"Lili", "last_name"=>"Song", "scopus_author_id"=>"56565864500"}, {"first_name"=>"Hairong", "last_name"=>"Yao", "scopus_author_id"=>"57190031921"}, {"first_name"=>"Liang", "last_name"=>"Zhang", "scopus_author_id"=>"56305617100"}, {"first_name"=>"Dongkui", "last_name"=>"Xu", "scopus_author_id"=>"57190034316"}, {"first_name"=>"Fangyuan", "last_name"=>"Gao", "scopus_author_id"=>"56565858100"}, {"first_name"=>"Qian", "last_name"=>"Li", "scopus_author_id"=>"57199178730"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84992176867", "sgr"=>"84992176867", "doi"=>"10.1371/journal.pone.0163460", "pui"=>"612774203", "pmid"=>"27658300", "issn"=>"19326203"}, "id"=>"40019cd9-ccd1-34d3-858f-55a97e0500cd", "abstract"=>"Epigenetic modulation is an important mechanism of miRNA dysregulation in cervical cancer. In this study, we firstly studied how this mechanism contributes to miR-375 downregulation in cervical cancer cells. Then, we further studied the association between miR-375 and MALAT1 (metastasis associated lung adenocarcinoma transcript 1) in epithelial mesenchymal transition (EMT) of the cancer cells. HPV-16 positive SiHa and CaSki cells were used as in vitro model. Our data showed that HPV-16 E6 positively modulated DNMT1 expression in both SiHa and CaSki cells. Knockdown of DNMT1 partly restored miR-375 levels in the cells. The following methylation-specific PCR (MSP) assay and qRT-PCR analysis showed that methylation was common in the promoter region of miR-375 in both SiHa and CaSki cells and demethylation partly restored miR-375 levels in the cells. Therefore, we infer that miR-375 is downregulated partly due to promoter hypermethylation mediated by DNMT1 in HPV-16 positive cervical cancer cells. Our bioinformatics analysis showed that MALAT1 has three putative binding sites with miR-375 and the following dual luciferase assay confirmed two of them. QRT-PCR analysis showed that miR-375 overexpression significantly reduced MALAT1 expression, while MALAT1 overexpression reversely suppressed miR-375 levels. Therefore, we infer that there is a reciprocal regulation between miR-375 and MALAT1 in the cells. In SiHa cells, miR-375 overexpression or MALAT1 siRNA partly restored E-cadherin expression, significantly reduced N-cadherin and also reduced invasion capacity of SiHa cells. Therefore, these results suggest that miR-375 and MALAT1 form a functional axis modulating EMT in cervical cancer.", "link"=>"http://www.mendeley.com/research/mir375-epigenetically-downregulated-hpv16-e6-mediated-dnmt1-upregulation-modulates-emt-cervical-canc", "reader_count"=>51, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Researcher"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>26, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>9}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Researcher"=>2, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>26, "Student > Master"=>5, "Other"=>2, "Student > Bachelor"=>9}, "reader_count_by_subject_area"=>{"Unspecified"=>5, "Biochemistry, Genetics and Molecular Biology"=>32, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>12, "Neuroscience"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>12}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>32}, "Unspecified"=>{"Unspecified"=>5}}, "group_count"=>3}

Scopus | Further Information

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