Analyses of DNA Methylation Involved in the Activation of Nuclear Karyopherin Alpha 2 Leading to Identify the Progression and Prognostic Significance Across Human Breast Cancer
Analyses of DNA Methylation Involved in the Activation of Nuclear Karyopherin Alpha 2 Leading to Identify the Progression and Prognostic Significance Across Human Breast Cancer
复制标题
DOI：
10.2147/cmar.s261290
复制
发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Wang, Hongwei
中科院分区：
文献类型：
--
作者：
Cui, Xiangrong;Jing, Xuan;Wang, Hongwei
背景资料：核转运蛋白α 2（KPNA 2）是一种核输入因子，在核质转运以及几种癌症中的细胞增殖、迁移和侵袭中起关键作用。然而，KPNA 2在乳腺癌中的作用以及潜在的分子机制尚未阐明。材料和方法：为了评估乳腺癌发生过程中的基因表达变化，KPNA 2表达进行了分析，使用基因表达谱交互分析和Oncomine分析。使用MEXPRESS工具、UALCAN癌症数据库和cBioPortal浏览器分析甲基化和表达之间的相关性。采用RT-PCR方法检测KPNA 2在乳腺癌组织中的表达及预后价值。采用甲基化特异性PCR检测KPNA 2甲基化水平。(1)KPNA 2在乳腺癌中的表达明显高于正常乳腺组织，并受启动子区DNA异常低甲基化的调控。(2)在乳腺癌患者中，KPNA 2表达较高的患者生存率较低。(3)乳腺癌组织中KPNA 2基因突变类型以错义突变为主。(4)结论：乳腺癌中KPNA 2基因启动子区的异常甲基化可能是KPNA 2基因异常表达的重要原因，KPNA 2基因的异常表达可能是乳腺癌预后不良的一个潜在指标。
Background: Karyopherin alpha 2 (KPNA2) is a nuclear import factor that plays a crucial role in nucleocytoplasmic transport, as well as cell proliferation, migration, and invasion in several cancers. However, the roles of KPNA2 in breast cancer as well as the underlying molecular mechanisms have not been elucidated.Materials and Methods: To evaluate gene expression alterations during breast carcinogenesis, KPNA2 expression was analyzed using the Gene Expression Profiling Interactive Analysis and Oncomine analyses. The correlation between methylation and expression was analyzed using the MEXPRESS tool, UALCAN cancer database, and cBioPortal browser. Then, the expression and prognostic value of KPNA2 were investigated by our own breast cancer samples using RT-PCR. KPNA2 methylation level was detected by methylation-specific PCR.Results: We obtained the following important results. (1) KPNA2 expression was significantly higher in breast cancer than normal samples and regulated by aberrant DNA hypomethylation of promoter region. (2) Among patients with breast cancer, those with higher KPNA2 expression had a lower survival rate. (3) The major mutation type of KPNA2 in breast cancer samples was missense mutation. (4) Homer1 was able to promote breast cancer progression may be through upregulating TPX2 expression.Conclusion: Our findings suggest that aberrant DNA hypomethylation of promoter regions contributes to the aberrant expression of KPNA2 in breast cancer, which might be a potential indicator of poor prognosis.