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

Increased expression of KPNA2 predicts unfavorable prognosis in ovarian cancer patients, possibly by targeting KIF4A signaling.
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DOI:
10.1186/s13048-021-00818-9
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发表时间:
2021-05-25
影响因子:
4
通讯作者:
Jing X
Jing X
中科院分区:
医学3区
文献类型:
--
作者:
Cui X;Wang H;Wu X;Huo K;Jing X

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核转运蛋白α-2 (KPNA2) 是核转运蛋白家族的一员,被证明负责货物蛋白的输入或输出。研究表明KPNA2与多种癌症的发生和预后相关,但KPNA2在卵巢癌中的作用及其潜在的分子机制仍不清楚。使用 GEPIA 和 Oncomine 分析研究 KPNA2 在卵巢癌中的表达和预后。通过cBioPortal数据库分析卵巢癌中KPNA2的突变。 KPNA2 表达的预后价值是通过我们自己的卵巢癌样本使用 RT-qPCR 进行评估的。随后,分别通过CCK-8和Transwell实验研究卵巢癌细胞的生长、迁移和侵袭。通过蛋白质印迹法测定KPNA2和KIF4A的蛋白水平。我们取得了以下重要成果。 (1)KPNA2和KIF4A在卵巢癌组织和细胞中过表达。 (2)在卵巢癌患者中,KPNA2过表达与较低的生存率相关。 (3)KPNA2的突变(R197*和S140F)会对蛋白质结构产生一定影响,进而可能导致蛋白质功能异常。 (4)KPNA2 konckdown抑制增殖、迁移、侵袭以及KIF4A的表达。 KPNA2 作为卵巢癌的致瘤基因,通过上调 KIF4A 加速肿瘤进展,这表明 KPNA2 可能是治疗和不良预后的一个有希望的指标。
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. 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. 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. 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.
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