MiR-26b/KPNA2 axis inhibits epithelial ovarian carcinoma proliferation and metastasis through downregulating OCT4.

Abstract

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.

• Authors: Jiaxin Lin, Lan Zhang, He Huang, Yongwen Huang, Long Huang, Jianhua Wang, Shuting Huang, Li He, Yun Zhou, Weihua Jia, Jingping Yun, Rongzhen Luo, Min Zheng
• Journal: Oncotarget (Oncotarget) Vol. 6 Issue 27 Pg. 23793-806 (Sep 15 2015) ISSN: 1949-2553 [Electronic] United States
• PMID: 26204489 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cadherins
• KPNA2 protein, human
• MIRN26A microRNA, human
• MicroRNAs
• Octamer Transcription Factor-3
• POU5F1 protein, human
• Vimentin
• alpha Karyopherins

Topics

• Animals
• Cadherins (biosynthesis)
• Carcinogenesis (genetics)
• Carcinoma, Ovarian Epithelial
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Disease Progression
• Disease-Free Survival
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• MicroRNAs (genetics)
• Neoplasm Recurrence, Local (genetics)
• Neoplasms, Glandular and Epithelial (genetics, mortality, pathology)
• Octamer Transcription Factor-3 (biosynthesis)
• Ovarian Neoplasms (genetics, mortality, pathology)
• Spheroids, Cellular (cytology)
• Tumor Cells, Cultured
• Vimentin (biosynthesis)
• alpha Karyopherins (genetics)