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

Xiangrong Cui,^1,* Xuan Jing,^2,* Xueqing Wu,¹ Jing Xu,³ Zhuang Liu,³ Kai Huo,⁴ Hongwei Wang<sup>3

1</sup>Reproductive Medicine Center, Children’s Hospital of Shanxi and Women Health Center of Shanxi, Affiliated of Shanxi Medical University, Taiyuan 030001, People’s Republic of China; ²Clinical Laboratory, Shanxi Province People’s Hospital, Affiliated of Shanxi Medical University, Taiyuan 030001, People’s Republic of China; ³Department of Hematology, 2nd Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, People’s Republic of China; ⁴Department of Breast Surgery, Shanxi Cancer Hospital, Taiyuan 030000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Hongwei Wang Tel +86-351-3360725
Email wanghongwei3360725@163.com

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.

Keywords: KPNA2, breast cancer, prognosis, methylation, TPX2