MiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4.
MiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4.
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MiR-26b/KPNA2轴通过下调OCT4抑制上皮性卵巢癌增殖和转移
DOI：
10.18632/oncotarget.4363
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发表时间：
2015-09-15
期刊：
影响因子：
--
通讯作者：
Zheng M
中科院分区：
文献类型：
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作者：
Lin J;Zhang L;Huang H;Huang Y;Huang L;Wang J;Huang S;He L;Zhou Y;Jia W;Yun J;Luo R;Zheng M
核转运蛋白α 2（KPNA 2）是一种在许多癌症中上调的核转运蛋白。我们以前的研究已经确定KPNA 2在上皮性卵巢癌（EOC）组织中的过表达，这预示着预后不良。然而，KPNA 2在EOC中过表达的机制仍不清楚。本研究旨在研究miRNA在KPNA 2失调中的作用。我们的研究结果表明，miR-26 b在EOC样本中下调，并与KPNA 2表达呈负相关。miR-26 b低表达与FIGO分期、分化程度、远处转移和复发风险相关。miR-26 b的下调预测EOC患者的无病生存率和总生存率较差。KPNA 2被验证为miR-26 b的直接靶点。KPNA 2的敲除或miR-26 b的异位表达可下调OCT 4、vimentin的表达，上调E-cadherin的表达。重新引入KPNA 2可部分消除miR-26 b诱导的抑制作用。我们进一步验证了miR-26 b/KPNA 2/OCT 4轴在体外和体内抑制EOC细胞活力、迁移能力和球体形成能力。总之，我们的研究结果表明，miR-26 b在EOC中下调，并直接靶向KPNA 2。miR-26 b/KPNA 2轴通过降低OCT 4表达抑制肿瘤增殖和转移，提示miR-26 b/KPNA 2/OCT 4轴在EOC的发生发展中具有重要作用。
Karyopherin alpha 2 (KPNA2) is a nuclear transport protein upregulated in many cancers. Our previous study has identified KPNA2 overexpression in epithelial ovarian carcinoma (EOC) tissues, which predicts poor prognosis. However, the mechanism of KPNA2 overexpression in EOC remains unclear. This study aimed to examine the role of miRNA in KPNA2 dysregulation. Our results showed that miR-26b was downregulated in EOC samples, and correlated inversely with KPNA2 expression. Low expression of miR-26b was associated with advanced FIGO stage, poor differentiation, higher risk of distant metastasis and recurrence. Downregulation of miR-26b predicted poor disease-free survival and overall survival in EOC patients. KPNA2 was validated as a direct target of miR-26b. Knockdown of KPNA2 or ectopic expression of miR-26b could downregulate OCT4, vimentin and upregulate E-cadherin. Reintroduction of KPNA2 partially abrogated the suppression effect induced by miR-26b. We further verified that miR-26b/KPNA2/OCT4 axis inhibited EOC cell viability, migratory ability and sphere-forming capacity in vitro and in vivo. In conclusion, our results reveal that miR-26b is downregulated in EOC, and directly targets KPNA2. miR-26b/KPNA2 axis suppresses tumor proliferation and metastasis through decreasing OCT4 expression, which is indicative of the important role of miR-26b/KPNA2/OCT4 axis in EOC carcinogenesis and progression.