WNT7A Regulation by miR-15b in Ovarian Cancer
Publication Date
May 19, 2016
Journal
PLOS ONE
Authors
James A. Mac Lean Ii, Mandy L. King, Hiroshi Okuda & Kanako Hayashi
Volume
11
Issue
5
Pages
e0156109
DOI
https://dx.plos.org/10.1371/journal.pone.0156109
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0156109
Web of Science
000376291100160
Scopus
84971246241
Mendeley
http://www.mendeley.com/research/wnt7a-regulation-mir15b-ovarian-cancer
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Mendeley | Further Information

{"title"=>"WNT7A regulation by miR-15b in ovarian cancer", "type"=>"journal", "authors"=>[{"first_name"=>"James A.", "last_name"=>"MacLean", "scopus_author_id"=>"7103304303"}, {"first_name"=>"Mandy L.", "last_name"=>"King", "scopus_author_id"=>"12239653000"}, {"first_name"=>"Hiroshi", "last_name"=>"Okuda", "scopus_author_id"=>"25625528700"}, {"first_name"=>"Kanako", "last_name"=>"Hayashi", "scopus_author_id"=>"7406143849"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84971246241", "sgr"=>"84971246241", "pui"=>"610471046", "issn"=>"19326203", "pmid"=>"27195958", "doi"=>"10.1371/journal.pone.0156109"}, "id"=>"11fdca9f-954e-3aa4-b055-374e451228a8", "abstract"=>"<p>WNT signaling is well known to play an important role in the regulation of development, cell proliferation and cell differentiation in a wide variety of normal and cancerous tissues. Despite the wealth of knowledge concerning when and where various <italic>WNT</italic> genes are expressed and downstream events under their control, there is surprisingly little published evidence of how they are regulated. We have recently reported that aberrant WNT7A is observed in serous ovarian carcinomas, and WNT7A is the sole ligand accelerating ovarian tumor progression through CTNNB1 (β-catenin)/TCF signaling in the absence of CTNNB1 mutations. In the present study, we report that <italic>WNT7A</italic> is a direct target of <italic>miR-15b</italic> in ovarian cancer. We showed that a luciferase reporter containing the putative binding site of <italic>miR-15b</italic> in the <italic>WNT7A</italic> 3’-UTR was significantly repressed by <italic>miR-15b</italic>. Mutation of the putative binding site of <italic>miR-15b</italic> in the <italic>WNT7A</italic> 3’-UTR restored luciferase activity. Furthermore, <italic>miR-15b</italic> was able to repress increased levels of TOPFLASH activity by WNT7A, but not those induced by S33Y. Additionally, <italic>miR-15b</italic> dose-dependently decreased <italic>WNT7A</italic> expression. When we evaluated the prognostic impact of <italic>WNT7A</italic> and <italic>miR-15b</italic> expression using TCGA datasets, a significant inverse correlation in which high-expression of <italic>WNT7A</italic> and low-expression of <italic>miR-15b</italic> was associated with reduced survival rates of ovarian cancer patients. Treatment with decitabine dose-dependently increased <italic>miR-15b</italic> expression, and silencing of <italic>DNMT1</italic> significantly increased <italic>miR-15b</italic> expression. These results suggest that <italic>WNT7A</italic> is post-transcriptionally regulated by <italic>miR-15b</italic>, which could be down-regulated by promoter hypermethylation, potentially via DNMT1, in ovarian cancer.</p>", "link"=>"http://www.mendeley.com/research/wnt7a-regulation-mir15b-ovarian-cancer", "reader_count"=>4, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Ph. D. Student"=>2, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Nursing and Health Professions"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Nursing and Health Professions"=>{"Nursing and Health Professions"=>1}}, "group_count"=>0}

Scopus | Further Information

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