ZNF300P1 Encodes a lincRNA that regulates cell polarity and is epigenetically silenced in type II epithelial ovarian cancer

Molecular Cancer

Research

James Scurry¹  Brian Gloss²  Maria Gonzalez²  Vita Lin²  Kim Moran-Jones³  Susan J Clark³  Robert L Sutherland³  Goli Samimi³  Neville F Hacker⁴ 

[1] Hunter Area Pathology Service, John Hunter Hospital, 2310New Lambton, NSW, Australia;Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, 370 Victoria Street, 2010, Darlinghurst, NSW, Australia;Kinghorn Cancer Centre and Cancer Research Program, Garvan Institute of Medical Research, 370 Victoria Street, 2010, Darlinghurst, NSW, Australia;St. Vincent’s Clinical School, University of New South Wales, 2010, Sydney, NSW, Australia;School of Women’s and Children’s Health, University of New South Wales, and Gynaecological Cancer Centre, Royal Hospital for Women, 2031, Sydney, NSW, Australia;

关键词: lincRNA;    Ovarian cancer;    Methylation;    Epigenetics;    ZNF300P1;    ZNF300;   

DOI  :  10.1186/1476-4598-13-3

 received in 2013-07-18, accepted in 2014-01-02,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundWe previously identified that the CpG island-associated promoter of the novel lincRNA ZNF300P1 (also known as LOC134466) is frequently hypermethylated and silenced in ovarian cancer tissues. However, the function of ZNF300P1 was unknown. In this report we demonstrate that ZNF300P1 is involved in the regulation of key cell cycle and cell motility networks in human ovarian surface epithelial cells, and may play a role in promoting metastasis in ovarian cancer cells.MethodsWe applied methylated DNA immunoprecipitation on whole genome promoter tiling arrays and Sequenom assays to examine methylation status of ZNF300P1 in multiple ovarian cancer cell lines, as well as in normal ovarian and ovarian tumor tissues. Transcript profiling was used to investigate the effects of ZNF300P1 suppression in ovarian cancer cells. We utilized siRNA knockdown in normal ovarian surface epithelial cells and performed cellular proliferation, migration and adhesion assays to validate and explore the profiling results.ResultsWe demonstrate that ZNF300P1 is methylated in multiple ovarian cancer cell lines. Loss of ZNF300P1 results in decreased cell proliferation and colony formation. In addition, knockdown of the ZNF300P1 transcript results in aberrant and less persistent migration in wound healing assays due to a loss of cellular polarity. Using an ex vivo peritoneal adhesion assay, we also reveal a role for ZNF300P1 in the attachment of ovarian cancer cells to peritoneal membranes, indicating a potential function of ZNF300P1 expression in metastasis of ovarian cancer cells to sites within the peritoneal cavity.ConclusionOur findings further support ZNF300P1 as frequently methylated in ovarian cancer and reveal a novel function for ZNF300P1 lincRNA expression in regulating cell polarity, motility, and adhesion and loss of expression may contribute to the metastatic potential of ovarian cancer cells.

【 授权许可】

Unknown   
© Gloss et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.