Abstract
The aim of the present study was to investigate the association between KDM3A expression and the clinicopathological parameters of patients with epithelial ovarian cancer (EOC). KDM3A expression was analyzed using immunohistochemistry in EOC tissue microarray containing 90 paired cases of EOC and matched normal control. The expression level of KDM3A protein in EOC tissues was significantly higher than that of adjacent normal control tissues. In addition, positive expression of KDM3A correlated with the metastases. Furthermore, Kaplan–Meier survival analysis showed that a high expression level of KDM3A resulted in a significantly poor prognosis of EOC patients. Knock-down of KDM3A could suppress both the proliferation, migration and invasion in vitro EOC cell lines OV-2008 and ES-2. Additionally, knock-down of KDM3A not only could enhance cellular apoptosis induced by Cisplatin and Paclitaxel, but also induced some pro-apoptotic genes expression. Our data is the first to demonstrate that increased KDM3A expression in EOC is significantly associated with metastases and poor prognosis; and that KDM3A promotes the proliferation, migration and invasion of EOC cells. Knock-down of KDM3A may be an important complement to EOC that is resistant or refractory to chemotherapy.
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References
Baker M (2015) Reproducibility crisis: blame it on the antibodies. Nature 521(7552):274–276
Beyer S, Kristensen MM, Jensen KS, Johansen JV, Staller P (2008) The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF. J Biol Chem 283(52):36542–36552
Chen H, Kluz T, Zhang R, Costa M (2010) Hypoxia and nickel inhibit histone demethylase JMJD1A and repress Spry2 expression in human bronchial epithelial BEAS-2B cells. Carcinogenesis 31(12):2136–2144
Chen C, Deng Y, Hua M, Xi Q, Liu R, Yang S, Liu J, Zhong J, Tang M, Lu S et al (2015) Expression and clinical role of TCTP in epithelial ovarian cancer. J Mol Histol 46(2):145–156
Cho HS, Toyokawa G, Daigo Y, Hayami S, Masuda K, Ikawa N, Yamane Y, Maejima K, Tsunoda T, Field HI et al (2012) The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene. Int J Cancer 131(3):E179–E189
Desai A, Xu J, Aysola K, Qin Y, Okoli C, Hariprasad R, Chinemerem U, Gates C, Reddy A, Danner O et al (2014) Epithelial ovarian cancer: an overview. World J Transl Med 3(1):1–8
Du ZM, Hu LF, Wang HY, Yan LX, Zeng YX, Shao JY, Ernberg I (2011) Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A. PLoS One 6(4):e19137
Groen RS, Gershenson DM, Fader AN (2015) Updates and emerging therapies for rare epithelial ovarian cancers: one size no longer fits all. Gynecol Oncol 136(2):373–383
Guo X, Shi M, Sun L, Wang Y, Gui Y, Cai Z, Duan X (2011) The expression of histone demethylase JMJD1A in renal cell carcinoma. Neoplasma 58(2):153–157
Holmseth S, Zhou Y, Follin-Arbelet VV, Lehre KP, Bergles DE, Danbolt NC (2012) Specificity controls for immunocytochemistry: the antigen preadsorption test can lead to inaccurate assessment of antibody specificity. J Histochem Cytochem 60(3):174–187
Jiang L, Liu R, Wang Y, Li C, Xi Q, Zhong J, Liu J, Yang S, Wang J, Huang M et al (2015) The role of Cyclin G1 in cellular proliferation and apoptosis of human epithelial ovarian cancer. J Mol Histol 46(3):291–302
Kaplan RM, Chambers DA, Glasgow RE (2014) Big data and large sample size: a cautionary note on the potential for bias. Clin Transl Sci 7(4):342–346
Krieg AJ, Rankin EB, Chan D, Razorenova O, Fernandez S, Giaccia AJ (2010) Regulation of the histone demethylase JMJD1A by hypoxia-inducible factor 1 alpha enhances hypoxic gene expression and tumor growth. Mol Cell Biol 30(1):344–353
Linderoth J, Ehinger M, Akerman M, Cavallin-Stahl E, Enblad G, Erlanson M, Jerkeman M (2007) Tissue microarray is inappropriate for analysis of BCL6 expression in diffuse large B-cell lymphoma. Eur J Haematol 79(2):146–149
Liu Z, Zhou S, Liao L, Chen X, Meistrich M, Xu J (2010) Jmjd1a demethylase-regulated histone modification is essential for cAMP-response element modulator-regulated gene expression and spermatogenesis. J Biol Chem 285(4):2758–2770
Mahajan K, Lawrence HR, Lawrence NJ, Mahajan NP (2014) ACK1 tyrosine kinase interacts with histone demethylase KDM3A to regulate the mammary tumor oncogene HOXA1. J Biol Chem 289(41):28179–28191
Meier DT, Entrup L, Templin AT, Hogan MF, Samarasekera T, Zraika S, Boyko EJ, Kahn SE (2015) Determination of optimal sample size for quantification of beta-cell area, amyloid area and beta-cell apoptosis in isolated islets. J Histochem Cytochem 63(8):663–673
Okada Y, Tateishi K, Zhang Y (2010) Histone demethylase JHDM2A is involved in male infertility and obesity. J Androl 31(1):75–78
Osawa T, Tsuchida R, Muramatsu M, Shimamura T, Wang F, Suehiro J, Kanki Y, Wada Y, Yuasa Y, Aburatani H et al (2013) Inhibition of histone demethylase JMJD1A improves anti-angiogenic therapy and reduces tumor-associated macrophages. Cancer Res 73(10):3019–3028
Park SJ, Kim JG, Son TG, Yi JM, Kim ND, Yang K, Heo K (2013) The histone demethylase JMJD1A regulates adrenomedullin-mediated cell proliferation in hepatocellular carcinoma under hypoxia. Biochem Biophys Res Commun 434(4):722–727
Sar A, Ponjevic D, Nguyen M, Box AH, Demetrick DJ (2009) Identification and characterization of demethylase JMJD1A as a gene upregulated in the human cellular response to hypoxia. Cell Tissue Res 337(2):223–234
Tee AE, Ling D, Nelson C, Atmadibrata B, Dinger ME, Xu N, Mizukami T, Liu PY, Liu B, Cheung B et al (2014) The histone demethylase JMJD1A induces cell migration and invasion by up-regulating the expression of the long noncoding RNA MALAT1. Oncotarget 5(7):1793–1804
Turan G, Usta CS, Usta A, Kanter M, Tavli L, Karacan M, Celik C, Eser M (2014) The expression of HER-2/neu (c-erbB2), survivin and cycline D1 in serous ovarian neoplasms: their correlation with clinicopathological variables. J Mol Histol 45(6):679–687
Vargas-Hernandez VM, Moreno-Eutimio MA, Acosta-Altamirano G, Vargas-Aguilar VM (2014) Management of recurrent epithelial ovarian cancer. Gland Surg 3(3):198–202
Wade MA, Jones D, Wilson L, Stockley J, Coffey K, Robson CN, Gaughan L (2015) The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer. Nucleic Acids Res 43(1):196–207
Yamada D, Kobayashi S, Yamamoto H, Tomimaru Y, Noda T, Uemura M, Wada H, Marubashi S, Eguchi H, Tanemura M et al (2012) Role of the hypoxia-related gene, JMJD1A, in hepatocellular carcinoma: clinical impact on recurrence after hepatic resection. Ann Surg Oncol 19(Suppl 3):S355–S364
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The work was finally supported by the Department of Gynaecology, The Affiliate Tumor Hospital of Xinjiang Medical University.
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Meili Pa and Gulimire Naizaer have contributed equally to the work.
"This article has been retracted at the request of the authors. The Editor-in-Chief has decided to retract this article, and the Publisher supports the decision of the Editor-in-Chief. This article has been found to contain plagiarized materials. Unpublished data was obtained from an unnamed source and has been used without permission. The owner of the data does not wish to be named in this retraction notice."
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Pa, M., Naizaer, G., Seyiti, A. et al. RETRACTED ARTICLE: KDM3A confers metastasis and chemoresistance in epithelial ovarian cancer. J Mol Hist 46, 511–518 (2015). https://doi.org/10.1007/s10735-015-9642-3
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DOI: https://doi.org/10.1007/s10735-015-9642-3