Analyses of DNA methylation involved in the activation of nuclear karyopherin alpha 2 leading to the progression and prognostic significance across human breast cancer

Abstract

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. 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 was 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 up-regulating TPX2 expression. Conclusions: 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.

microRNA‐17 is a tumor suppressor in oral squamous cell carcinoma and is repressed by LSD1

“…In a review by Christiansen and Dyrskjot, 2013, KPNA2 has been documented as a potential biomarker in multiple cancers, and its high levels observed in cancer tissues have been correlated to adverse characteristics of patients, indicating its role in carcinogenesis (Christiansen & Dyrskjot, 2013). KPNA2 expression was also significantly higher in breast cancer than that in normal samples and regulated by aberrant DNA hypomethylation of the promoter region (Cui et al., 2020). In addition, KPNA2 silencing exerted anti‐proliferative, pro‐apoptotic, and anti‐migratory effects on the tongue squamous cell carcinoma cells (Gao et al., 2016).…”

DNA methylation and breast cancer: A way forward (Review)

“…Epigenetic alteration Gene Potential clinical utility Ref. In all studies, the subjects were female, apart from Cui et al (31), where subjects were female/male.…”

“…The association between KPNA2 expression and prognosis in BC was evaluated using overall survival, relapse-free survival, distant metastasis-free survival and post-progression survival time curves in patients with BC. KPNA2 may serve as a potential indicator of poor prognosis, as promoter hypomethylation of the gene was reported in patients with a lower survival rate (31,32).…”