Increased expression of KPNA2 predicts unfavorable prognosis in ovarian cancer patients, possibly by targeting KIF4A signaling

Abstract

Background Karyopherin α-2 (KPNA2) is a member of karyopherin family, which is proved to be responsible for the import or export of cargo proteins. Studies have determined that KPNA2 is associated with the development and prognosis of various cancers, yet the role of KPNA2 in ovarian carcinoma and its potential molecular mechanisms remains unclear. Materials and methods The expression and prognosis of KPNA2 in ovarian cancer was investigated using GEPIA and Oncomine analyses. Mutations of KPNA2 in ovarian cancer were analyzed by cBioPortal database. The prognostic value of KPNA2 expression was evaluated by our own ovarian carcinoma samples using RT-qPCR. Subsequently, the cell growth, migration and invasion of ovarian cancer cells were investigated by CCK-8 and transwell assay, respectively. The protein levels of KPNA2 and KIF4A were determined by western blot. Results We obtained the following important results. (1) KPNA2 and KIF4A wereoverexpressed in ovairan cancer tissues and cells. (2) Among patients with ovarian cancer, overexpressed KPNA2 was associated with lower survival rate. (3) Mutations (R197* and S140F) in KPNA2 will have some influences on protein structure, and then may cause protein function abnormal. (4) KPNA2 konckdown inhibited proliferation, migration, invasion, as well as the expression of KIF4A. Conclusion KPNA2, as a tumorigenic gene in ovarian cancer, accelerated tumor progression by up-regulating KIF4A, suggesting that KPNA2 might be a hopeful indicator of treatment and poor prognosis.

Evaluation of the role of KPNA2 mutations in breast cancer prognosis using bioinformatics datasets

“…CDK1, also co-expressed with KPNA2, promotes G2/M cell cycle transition and has previously been reported in hepatocellular carcinomas [8]. Moreover, KPNA2 overexpression in ovarian cancer was recently linked to KIF4F signalling upregulation accelerating tumour progression [38,39]. ZW10 interacting kinetochore protein (ZWINT) and Epithelial cell transforming 2 (ECT), both mitotic checkpoint proteins, have been shown to contribute to poor prognosis across multiple cancer types including glioblastoma [40].…”

Decreased Expression of Karyopherin-α 1 is Related to the Malignant Degree of Cervical Cancer and is Critical for the Proliferation of Hela Cells

“…In recent years, there have been many studies demonstrating that the aberrant expression of KPNA2 is often associated with the progression and development of multiple tumors. Cui, et al proved that the increased expression of KPNA2 accelerated ovarian tumor progression by targeting KIF4A signaling ( 27 ). Zeng, et al reported that high expression of KPNA2 promoted the development of bladder cancer through interactions with CBX8 ( 28 ).…”

Comprehensive analysis of karyopherin alpha family expression in lung adenocarcinoma: Association with prognostic value and immune homeostasis

“…High KPNA2 expression in melanoma was linked to poor OS and disease-free survival (DFS) ( Yang et al, 2020 ). High expression of KPNA2 has been identified in ovarian carcinoma and cervical cancer, which was associated with poor prognosis ( Cui et al, 2021 ; Wang et al, 2021 ). High KPNA4 expression in liver cancer was shown to be associated with poor OS in patients ( Xu et al, 2021 ).…”