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山东大学学报(医学版) ›› 2015, Vol. 53 ›› Issue (6): 48-53.doi: 10.6040/j.issn.1671-7554.0.2014.560

• 基础医学 • 上一篇    下一篇

沉默PADI4基因对卵巢癌细胞系OVCAR3的作用

周静1,2, 常晓天2, 周婷2, 崔莹莹2, 张蓓2, 荣风年2   

  1. 1. 山东大学医学院, 山东 济南 250012;
    2. 山东大学附属千佛山医院妇产科, 山东 济南 250014
  • 收稿日期:2014-10-10 修回日期:2015-03-06 出版日期:2015-06-10 发布日期:2015-06-10
  • 通讯作者: 荣风年。 E-mail:fnrong@163.com E-mail:fnrong@163.com
  • 基金资助:
    山东省自然科学基金(ZR2013HM037)

Effects of PADI4 silence on ovarian cancer cell line OVCAR3

ZHOU Jing1,2, CHANG Xiaotian2, ZHOU Ting2, CUI Yingying2, ZHANG Bei2, RONG Fengnian2   

  1. 1. School of Medicine, Shandong University, Jinan 250012, Shandong, China;
    2. Department of Gynecology and Obstetrics, Qianfoshan Hospital Affiliated to Shandong University, Jinan 250014, Shandong, China
  • Received:2014-10-10 Revised:2015-03-06 Online:2015-06-10 Published:2015-06-10

摘要: 目的 探讨抑制肽酰基精氨酸脱亚氨酶4(PADI4)对卵巢癌细胞系OVCAR3的影响。方法 PADI4-siRNA组和阴性对照组siRNA分别转染卵巢癌细胞OVCAR3,采用实时定量PCR及Western Blotting检测PADI4、p53和p21的表达, AnnexinⅤ-PE/7-AAD双染和transwell小室法分别检测细胞凋亡、侵袭和迁移的情况。结果 与阴性对照组相比,PADI4-siRNA组的OVCAR3细胞中PADI4表达降低,且其凋亡细胞比例明显增加(P<0.05),细胞侵袭能力明显减弱(P<0.01),但细胞趋化能力没有明显变化。PADI4-siRNA组p53表达较阴性对照组降低,但p21表达并没有降低。结论 沉默PADI4影响卵巢癌细胞OVCAR3凋亡和侵袭特性,提示PADI4参与调控卵巢癌细胞恶性生物学行为。

关键词: 肽酰基精氨酸脱亚氨酶4, 卵巢肿瘤, 细胞凋亡, 侵袭, 迁移

Abstract: Objective To investigate the effects of PADI4 silence on ovarian cancer cell line OVCAR3. Methods OVCAR3 cells were transfected with siRNA of PADI4-siRNA group and negative control group in vitro respectively. The expressions of PADI4, p53 and p21 were detected with real-time PCR and Western blotting. Cell apoptosis, invasion and migration were measured with AnnexinV-PE/7-AAD assay and Transwell assay. Results Compared with that of the negative control group, PADI4 expression of OVCAR3 cells in PADI4-siRNA group decreased significantly, the invasion ability and apoptotic ratio also reduced (Pa<0.05, Pi<0.01). However, the chemotaxis ability showed no change. Compared with that of the negative control group, expression of p53 decreased, while p21 expression remained unchanged. Conclusion PADI4 silence altered the apoptosis and invasion abilities of ovarian cancer cell OVCAR3, demonstrating that PADI4 plays an important role in the control of malignant biological behavior of ovarian cancer.

Key words: Invasion, Apoptosis, Migration, Ovarian tumor, Peptidylarginine deiminase 4

中图分类号: 

  • R711.75
[1] Jemal A, Siegel R, Xu J, et al. Cancer statistics[J]. CA Cancer J Clin, 2010, 60(5): 277-300.
[2] Wang L, Chang X, Yuan G, et al. Expression of peptidylarginine deiminase type 4 in ovarian tumors[J]. Int J Biol Sci, 2010, 6(5): 454-464.
[3] Liu GY, Liao YF, Chang WH, et al. Overexpression of peptidylarginine deiminase IV features in apoptosis of haematopoietic cells[J]. Apoptosis, 2006, 11(2): 183-196.
[4] Yang Lv, Yan Xia, Yaohua Wang, et al. Expression of PADI4 in hepatocellular carcinoma[J]. Chinese-German Journal of Clinical Oncology, 2009, 8(8):453-455. doi: 10.1007/s10330-009-0058-y.
[5] Chang X, Han J. Expression of peptidylarginine deiminase type 4 (PAD4) in various tumors[J]. Mol Carcinog, 2006, 45(3): 183-196.
[6] Chang X, Hou X, Pan J, et al. Investigating the pathogenic role of PADI4 in oesophageal cancer[J]. Int J Biol Sci, 2011, 7(6): 769-781
[7] Chang X, Han J, Pang L, et al. Increased PADI4 expression in blood and tissues of patients with malignant tumors[J]. BMC Cancer, 2009, 9: 40. doi: 10.1186/1471-2407-9-40.
[8] Tanikawa C, Ueda K, Nakagawa H, et al. Regulation of protein citrullination through p53/PADI4 network in DNA damage response[J]. Cancer Res, 2009, 69(22): 8761-8769.
[9] 罗祎, 姚珍薇, 杨雅莹, 等. 人端粒酶逆转录酶基因 siRNA质粒的构建及其对不同p53状态卵巢癌细胞生长和凋亡的影响[J]. 中国生物制品学杂志, 2013, 26(6): 780-791. LUO Yi, YAO Zhenwei, YANG Yaying, et al. Contstruction of siRNA plasmid for human telomerase reverse transcriptase gene and its effect on growth and apoptosis of ovarian cancer cells in presence or absence of p53[J]. Chinese Journal of Biologicals, 2013, 26(6): 780-791.
[10] Mirza A, Wu Q, Wang L, et al. Global transcriptional program of p53 target genes during the process of apoptosis and cell cycle progression[J]. Oncogene, 2003, 22(23): 3645-3654.
[11] Zuckerman V, Wolyniec K, Sionov RV, et al. Tumour suppression by p53: the importance of apoptosis and cellular senescence[J]. J Pathol, 2009, 219(1): 3-15.
[12] Lee JH, Lee SY, Lee JH, et al. p21WAF1 is involved in interferon-β-induced attenuation of telomerase activity and human telom-erase reverse transcriptase (hTERT) expression in ovarian cancer[J]. Mol Cells, 2010, 30(4): 327-333.
[13] Deplus R, Denis H, Putmans P, et al. Citrullination of DNMT3A by PADI4 regulates its stability and controls DNA methylation[J]. Nucleic Acids Res, 2014, 42(13): 8285-8296.
[14] Yao H, Li P, Venters BJ, et al. Histone Arg modifications and p53 regulate the expression of OKL38, a mediator of apoptosis[J]. J Biol Chem, 2008, 283(29): 20060-20068.
[15] Li P, Yao H, Zhang Z, et al. Regulation of p53 target gene expression by peptidylarginine deiminase[J]. Mol Cell Biol, 2008, 28(15): 4745-4758.
[16] Kim EH, Kim IH, Ha JA, et al. Antistress effect of red ginseng in brain cells is mediated by TACE repression via PADI4[J]. J Ginseng Res, 2013, 37(3): 315-323.
[17] Chang X, Fang K. PADI4 and tumourigenesis[J]. Cancer Cell Int, 2010, 10:7. doi: 10.1186/1475-2867-10-7.
[18] Guo H, Wu F, Wang Y, et al. Overexpressed ubiquitin ligase cullin 7 in breast cancer promotes cell proliferation and invasion via down-regulating p53[J]. Biochem Biophys Res Commun, 2014, 450(4): 1370-1376.
[19] 周静, 郑亚冰, 闫莉, 等. 雌激素及顺铂对卵巢癌细胞A2780PADI4的表达及其细胞增殖的影响[J]. 山东大学学报:医学版, 2014, 52(12): 30-34. ZHOU Jing, ZHENG Yabing, YAN Li, et al. The effects of estrogen and cis-platinum on PADI4 expression and cell proliferation in ovarian cancer cell line A2780[J]. Journal of Shandong University (Health Sciences), 2014, 52(12): 30-34.
[20] Spillman MA, Manning NG, Dye WW, et al. Tissue-specific pathways for estrogen regulation of ovarian cancer growth and metastasis[J]. Cancer Res, 2010, 70(21): 8927-8936.
[21] Hua K, Feng W, Cao Q, et al. Estrogen and progestin regulate metastasis through the PI3K/AKT pathway in human ovarian cancer[J]. Int J Oncol, 2008, 33(5): 959-967.
[22] Park SH, Cheung LW, Wong AS, et al. Estrogen regulates snail and slug in the downregulation of E-cadherin and induces metastatic potential of ovarian cancer cells through estrogen receptor alpha[J]. Mol Endocrinol, 2008, 22(9): 2085-2098.
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