[1]孙冰纯,洪龙年,廖靖,等.miR-486-3p通过调控血小板衍生生长因子相关蛋白1抑制卵巢癌细胞增殖的研究[J].中国计划生育和妇产科,2019,(7):77-81.
　SUN Bing-chun,HONG Long-nian,LIAO Jing,et al.Inhibition of proliferation of ovarian cancer cells by regulation of platelet-derived growth factor-associated protein 1 by miR-486-3p[J].Chinese Journal of Family Planning & Gynecotokology,2019,(7):77-81.
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miR-486-3p通过调控血小板衍生生长因子相关蛋白1抑制卵巢癌细胞增殖的研究
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《中国计划生育和妇产科》[ISSN:1674-4020/CN:51-1708/R]

卷:
期数:
2019年7期
页码:
77-81
栏目:
论著与临床
出版日期:
2019-06-25

文章信息/Info

Title:
Inhibition of proliferation of ovarian cancer cells by regulation of platelet-derived growth factor-associated protein 1 by miR-486-3p
作者:
孙冰纯; 洪龙年; 廖靖; 范可心; 黄金智*
广东医科大学附属医院妇产科
Author(s):
SUN Bing-chun;  HONG Long-nian;  LIAO Jing;  FAN Ke-xin;  HUANG Jin-zhi*
Department of Obstetrics and Gynecology, Affiliated Hospital of Guangdong Medical University, Zhanjiang Guangdong 524001, P.R.China
关键词:
miR-486-3p; PDAP 1; 卵巢癌; 增殖
Keywords:
miR-486-3p;  PDAP 1;  ovarian cancer;  proliferation
分类号:
R 737
摘要:
目的探讨miR-486-3p和血小板衍生生长因子相关蛋白1（platelet-derived growth factor-associated protein 1, PDAP 1）基因在卵巢癌中的表达情况以及它们的相互调控关系。方法回顾性分析2015~2017年在广东医科大学第一附属医院住院并经临床和病理证实为卵巢癌的8例患者临床卵巢癌肿瘤组织标本，收集同期4例卵巢非恶性病变者(阴性对照组) 的标本，通过荧光实时定量PCR和免疫印迹技术，分析miR-486-3p和PDAP 1在卵巢癌的表达情况。采用生物信息学和双荧光素酶实验证实它们之间的调控关系，并研究它们对卵巢癌细胞增殖的影响。结果miR-486-3p在卵巢癌细胞和肿瘤组织中均出现显著下调(P<005)，而PDAP 1则过表达(P<005)。它们的表达量间呈负相关关系（r=-082,P<005），进一步研究证实PDAP 1是miR-486-3p的靶点。上调miR-486-3p或抑制PDAP 1的表达均可导致卵巢癌细胞增殖受抑。结论以miR-486-3p和PDAP 1为靶点的基因治疗有望应用于卵巢癌治疗。
Abstract:
Objective To clarify the expression and interaction of miR-486-3p and PDAP 1 gene in ovarian cancer. MethodsRetrospective analyzed the tumor tissue specimens from 8 patients who were hospitalized in Affiliated Hospital of Guangdong Medical University and clinically and pathologically confirmed as ovarian cancer in 2015~2017, and collected specimens of 4 patients with non-maglignant ovarian cancer (negative control group).The expression of miR-486-3p and PDAP 1 in ovarian cancer was analyzed by real-time quantitative PCR and western blotting. Bioinformatics and dual luciferase assays were used to confirm their regulatory relationships. The impact on the proliferation of ovarian cancer cells of miR-486-3p and PDAP 1 were further investigated. ResultsMiR-486-3p was significantly down-regulated in ovarian cancer cells and tumor tissues(P<005), whereas PDAP 1 was over-expressed(P<005). There was a negative correlation between their expressions. Further studies confirmed that PDAP 1 is the target of miR-486-3p. Up-regulation of miR-486-3p or inhibition of PDAP 1 expression can lead to suppressed proliferation of ovarian cancer cells. ConclusionGene therapy targeting miR-486-3p and PDAP 1 is expected to be used for the treatment of ovarian cancer.

参考文献/References:

［1］SIEGEL R L, MILLER K D, JEMAL A. Cancer statistics, 2015 ［J］. CA-A Cancer Journal for Clinicians, 2015, 65(1): 5-29. ［2］AGARWAL V, BELL G W, NAM J W, et al. Predicting effective microRNA target sites in mammalian mRNAs ［J］. eLife, 2015, 4：e05005. ［3］WONG N, WANG Xiaowei. miRDB: an online resource for microRNA target prediction and functional annotations ［J］. Nucleic Acids Research, 2015, 43(Database issue): D146-D152. ［4］DING J, LI X, HU H. Tarpmir:a new approach for microrna target site prediction ［J］. Bioinformatics, 2016, 32(18): 2768-2775. ［5］CHEN Caifu, RIDZON D A, BROOMER A J, et al. Real-time quantification of microRNAs by stem-loop RT-PCR ［J］. Nucleic Acids Research, 2005, 33(20): e179. ［6］Stefania, Oliveto, Marilena, et al. Role of microRNAs in translation regulation and cancer ［J］. World Journal of Biological Chemistry, 2017, 8(1): 45-56. ［7］RETAMALES-ORTEGA R, OROSTICA L, VERA C A, et al. Role of nerve growth factor (NGF) and miRNAs in epithelial ovarian cancer ［J］. International Journal of Molecular Sciences, 2017, 18(3)：e507. ［8］ Chen Z, Yu T, Cabay R, et al. Mir-486-3p, mir-139-5p, and mir-21 as biomarkers for the detection of oral tongue squamous cell carcinoma ［J］. Biomark Cancer, 2017, 9: 1-8. ［9］ZENG M, MA W, ZHENG W. Bioinformatics analysis of microrna comprehensive regulatory network in b-cell acute lymphoblastic leukemia ［J］. Zhonghua xue Ye Xue Za Zhi, 2016, 37(7): 585-590. ［10］PLAISIER C L, O'BRIEN S, BERNARD B A, et al. Causal mechanistic regulatory network for glioblastoma deciphered using systems genetics network analysis ［J］. CELL SYSTEMS, 2016, 3(2): 172-186. ［11］JIANG Xiu-mei, DU Lu-tao, DUAN Wei-li, et al. Serum microRNA expression signatures as novel noninvasive biomarkers for prediction and prognosis of muscle-invasive bladder cancer ［J］. Oncotarget, 2016, 7(24): 36733-36742. ［12］YE Hai-qiong, YU Xiao-lan, XIA Ji-yi, et al. MiR-486-3p targeting ECM1 represses cell proliferation and metastasis in cervical cancer ［J］. Biomedicine & Pharmacotherapy, 2016, 80:109-114. ［13］ Venkatesan N, Deepa P, Khetan V, et al. Computational and in vitro investigation of mirna-gene regulations in retinoblastoma pathogenesis: Mirna mimics strategy ［J］. BioinformBiol Insights, 2015, 9: 89-101. ［14］FOTINOS A, NAGARAJAN N, MARTINS A S, et al. Bone morphogenetic protein-focused strategies to induce cytotoxicity in lung cancer cells ［J］. Anticancer Research, 2014, 34(5): 2095-2104. ［15］SWIERNIAK M, WOJCICKA A, CZETWERTYNSKA M, et al. In-depth characterization of the microRNA transcriptome in normal thyroid and papillary thyroid carcinoma ［J］. The Journal of Clinical Endocrinology and Metabolism, 2013, 98(8): E 1401-E 1409. ［16］HUMMEL R, WANG Tingting, WATSON D I, et al. Chemotherapy-induced modification of microRNA expression in esophageal cancer ［J］. Oncology Reports, 2011, 26(4): 1011-1017. ［17］MASLIAH-PLANCHON J, PASMANT E, LUSCAN A, et al. MicroRNAome profiling in benign and malignant neurofibromatosis type 1-associated nerve sheath tumors: evidences of PTEN pathway alterations in early NF1 tumorigenesis ［J］. BMC Genomics, 2013, 14: 473. ［18］MOSAKHANI N, SARHADI V, BORZE I, et al. Microrna profiling differentiates colorectal cancer according to krasstatus ［J］. Genes Chromosomes & Cancer, 2012, 51(1): 1-9. ［19］HUANG Y, LIN K, CHEN H, et al. Identification of postoperative prognostic microrna predictors in hepatocellular carcinoma ［J］. PLOS One, 2012, 7(5): e 37188. ［20］ Weston V, Wei W, Stankovic T, et al. Synergistic action of dual igf1/r and mekinhibition sensitizes childhood acute lymphoblastic leukemia (all) cells to cytotoxic agents and involves downregulation of stat6 and pdap1 ［J］. Exp Hematol, 2018,63:52-63. ［21］SHARMA V K, SINGH A, SRIVASTAVA S K, et al. Increased expression of platelet-derived growth factor associated protein-1 is associated with PDGF-B mediated glioma progression ［J］. International Journal of Biochemistry & Cell Biology, 2016, 78: 194-205. ［22］MARIMUTHU A, SUBBANNAYYA Y, SAHASRABUDDHE N A, et al. SILAC-based quantitative proteomic analysis of gastric cancer secretome ［J］. Proteomics Clinical Applications, 2013, 7(5/6, SI): 355-366. ［23］CHOI S Y, JANG J H, KIM K R. Analysis of differentially expressed genes in human rectal carcinoma using suppression subtractive hybridization ［J］. Clinical and Experimental Medicine, 2011, 11(4): 219-226. ［24］刘玲．Mirna-mrna差异表达与卵巢癌多药耐药关系的研究 ［D］．南宁：广西医科大学，2014．

备注/Memo

备注/Memo:
湛江市科技攻关计划项目(项目编号：2015B01045)；广东医科大学科研基金项目(项目编号：2xk14053)
更新日期/Last Update: 2019-07-25