Downregulation of tumor suppressor gene ribonuclease T2 and gametogenetin binding protein 2 is associated with drug resistance in ovarian cancer.

Downregulation of tumor suppressor gene ribonuclease T2 and gametogenetin binding protein 2 is associated with drug resistance in ovarian cancer.
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肿瘤抑制基因核糖核酸酶 T2 和配子生成素结合蛋白 2 的下调与卵巢癌的耐药性相关。

DOI:
10.3892/or.2014.3175
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发表时间:
2014-07
期刊:
影响因子:
4.2
通讯作者:
Li Li
Li Li
中科院分区:
医学3区
文献类型:
--
作者:
Li Danrong;Wang Qi;Zhang Wei;Li Li

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核糖核酸酶T2(RNASET 2)和配子生成素结合蛋白2(GGNBP 2)是在卵巢癌和其他类型的癌症中表达下调的肿瘤抑制基因。然而,这些基因编码的蛋白质是否与耐药性有关却鲜有研究。利用实时定量聚合酶链反应,在本研究中,我们发现,RNASET 2和GGNBP 2 mRNA水平显着低于在A2780-CBP(卡铂耐药)和A2780-DDP(顺铂耐药)卵巢癌细胞比在亲本A2780细胞,并在耐药卵巢癌组织中下调与他们的药物敏感的同行。这些发现与从基因表达综合谱数据库检索的微阵列数据确定的表达谱一致。因此,我们假设RNASET 2和GGNBP 2的下调参与卵巢癌耐药性的发展。因此,对这两个基因进行了全面的生物信息学分析,包括基因/蛋白质-基因/蛋白质相互作用、生物过程注释、共表达基因的途径富集和microRNA-mRNA分析。综合结果表明,RNASET 2和GGNBP 2通过与参与广泛生物过程和途径的许多microRNA、基因和蛋白质直接或间接相互作用,导致卵巢癌的耐药性。本研究中提供的信息为进一步研究RNASET 2和GGNBP 2的耐药性相关功能提供了见解。
Ribonuclease T2 (RNASET2) and gametogenetin binding protein 2 (GGNBP2) are tumor suppressor genes whose expression is downregulated in ovarian and other types of cancer. However, whether the proteins encoded by these genes are associated with drug resistance has rarely been studied. Using real-time quantitative polymerase chain reaction, in the present study we showed that RNASET2 and GGNBP2 mRNA levels were significantly lower in A2780-CBP (carboplatin-resistant) and A2780-DDP (cisplatin-resistant) ovarian cancer cells than in the parental A2780 cells and were downregulated in drug-resistant ovarian cancer tissues compared with their drug-sensitive counterparts. These findings were consistent with the expression profiles determined from microarray data retrieved from the Gene Expression Omnibus Profiles database. Accordingly, we hypothesized that the downregulation of RNASET2 and GGNBP2 is involved in the development of drug resistance in ovarian cancer. A comprehensive bioinformatics analysis of the two genes was therefore conducted, including gene/protein-gene/protein interactions, biological process annotation, pathway enrichment of co-expressed genes and microRNA-mRNA analyses. The integrated results suggested that RNASET2 and GGNBP2 contributed to drug resistance in ovarian cancer, via direct or indirect interactions with a number of microRNAs, genes and proteins involved in a wide range of biological processes and pathways. The information provided in the present study provides insight for further investigations of the drug resistance-related functions of RNASET2 and GGNBP2.
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