基于生物信息学分析MYBL2在卵巢癌耐药性中的作用及其机制

许丁文; 雒森; 袁红网; 严慧深; 金超超; 姚伟娟<sup>*</sup>

引用本文:	许丁文,雒森,袁红网,严慧深,金超超,姚伟娟.基于生物信息学分析MYBL2在卵巢癌耐药性中的作用及其机制[J].中国现代应用药学,2020,37(10):1166-1170.
	XU Dingwen,LUO Sen,YUAN Hongwang,YAN Huishen,JIN Chaochao,YAO Weijuan.Influence of MYBL2 on Drug Resistance in Ovarian Cancer and It's Underlying Mechanism Based on Bioinformatics Analysis[J].Chin J Mod Appl Pharm(中国现代应用药学),2020,37(10):1166-1170.

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基于生物信息学分析MYBL2在卵巢癌耐药性中的作用及其机制
许丁文¹, 雒森¹, 袁红网¹, 严慧深¹, 金超超², 姚伟娟³
1.扬州市职业大学医学院临床教研室, 江苏扬州 225009;2.黄石市中医医院肿瘤科, 湖北黄石 435000;3.北京大学基础医学院生理学与病理生理学系, 北京 100191

摘要:

目的研究分析MYBL2与卵巢癌耐药性之间的关系。方法运用GEPIA在线工具分析MYBL2在正常卵巢组织与卵巢癌组织中的表达差异，运用km-plot分析卵巢癌患者关于MYBL2的总生存曲线；基于GEO Profiles数据库分析MYBL2在顺铂敏感性与顺铂耐药性的卵巢癌细胞株中的表达差异。综合运用基因互作分析、基因通路富集和文本挖掘、miRNA-mRNA相互作用分析等生物信息学方法进一步证明MYBL2调节卵巢癌耐药性及探索其内在机制。结果卵巢癌组织中MYBL2的表达显著高于正常卵巢组织，高表达MYBL2与卵巢癌患者低生存率有关，顺铂耐药的卵巢癌细胞株MYBL2表达显著高于顺铂敏感的卵巢癌细胞株，与MYBL2具有高度关联性的基因大部分与卵巢癌耐药性有关；基因通路富集对与MYBL2相关联的基因分析发现，细胞周期富集程度最高；文本挖掘显示，除了细胞周期外，基因表达、细胞增殖、凋亡过程等生物过程与MYBL2蛋白、卵巢癌、肿瘤耐药性具有显著的关联性；miRNA-mRNA互作分析发现，靶向于MYBL2的12个miRNA皆与卵巢癌耐药性或肿瘤发生发展有关。结论 MYBL2与卵巢癌的耐药性有关，而且有可能是通过调节细胞周期而参与到卵巢癌耐药性中。

关键词: MYBL2 卵巢癌耐药性生物信息学

DOI：10.13748/j.cnki.issn1007-7693.2020.10.003

分类号:R966

基金项目:国家自然科学基金项目（31570938）；江苏省高等学校自然科学面上项目（18KJD360003）；扬州市职业大学校级科研项目（2018ZR27）；江苏省大学生创新训练资助项目（201911462011Y）

Influence of MYBL2 on Drug Resistance in Ovarian Cancer and It's Underlying Mechanism Based on Bioinformatics Analysis

XU Dingwen¹, LUO Sen¹, YUAN Hongwang¹, YAN Huishen¹, JIN Chaochao², YAO Weijuan³

1.Department of Clinic, School of Medicine, Yangzhou Polytechnic College, Yangzhou 225009, China;2.Department of Oncology, Huangshi Hospital of Traditional Chinese Medicine, Huangshi 435000, China;3.Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China

Abstract:

OBJECTIVE To analyze the association of MYBL2 with drug resistance in ovarian cancer. METHODS Used GEPIA online tool to detect the mRNA expression of MYBL2 in normal ovary tissue and ovarian cancer. Used GEO profiles database to analyze the mRNA expression of MYBL2 in cisplatin sensitive and cisplatin resistant A2780 cell lines. Km-plot was used to perform OS survival rate. Comprehensive bioinformatic analyses were performed through gene interaction analysis, genetic pathway enrichment analysis, text mining and miRNA-mRNA interaction analysis to further prove MYBL2 regulated ovarian cancer drug resistance and its underlying mechanism. RESULTS The expression of MYBL2 was higher in ovarian cancer compared with normal ovary. The expression of MYBL2 was higher in cisplatin resistant A2780 compared with cisplatin resistant A2780. Most proteins closely interacted with MYBL2 were associated with drug resistance in ovarian cancer. Using genetic pathway enrichment to analyze genes interacted with MYBL2, found the most enriched pathway was cell cycle. Text mining showed besides cell cycle, gene expression, cell proliferation, apoptotic process were also significantly associated with MYBL2, ovarian cancer and drug resistance. miRNA-mRNA interaction analysis found that all 12 miRNAs targeted to MYBL2 are associated with ovarian cancer drug resistance or tumorigenesis. CONCLUSION MYBL2 is associated with ovarian cancer drug resistance, and possibly by regulating cell cycle.

Key words: MYBL2 ovarian cancer drug resistance bioinformatics