title: 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.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Gynecology, Guangzhou, P. R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Gynecology, Guangzhou, P. R. China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Gynecology, Guangzhou, P. R. China.
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Oncology, The Second Affiliated Hospital, Nanchang University, Nanchang, P. R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Huang
authors.affiliation: Cardiovascular Department, Second People's Hospital of Guangdong Province, Guangzhou, P. R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Gynecology, Guangzhou, P. R. China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Gynecology, Guangzhou, P. R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Jingping
authors.initials: J
authors.lastname: Yun
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China.
authors.forename: Rongzhen
authors.initials: R
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Oncology in South China, Guangzhou, P. R. China.|Collaborative Innovation Center for Cancer Medicine, Guangzhou, P. R. China.|Department of Gynecology, Guangzhou, P. R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis; D063646:Carcinogenesis / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D018874:Spheroids, Cellular / Q000166:cytology; D014407:Tumor Cells, Cultured; D014746:Vimentin / Q000096:biosynthesis; D028901:alpha Karyopherins / Q000235:genetics*
chemical_list: D015820:Cadherins; D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; D014746:Vimentin; D028901:alpha Karyopherins; C490630:KPNA2 protein, human; C528163:MIRN26 microRNA, human; C494173:POU5F1 protein, human
keywords: KPNA2; OCT4; epithelial ovarian cancer; miR-26b