miR-603 promotes glioma cell growth via Wnt/β-catenin pathway by inhibiting WIF1 and CTNNBIP1

Mian Guo; Xiaoming Zhang; Guangzhi Wang; Jiahang Sun; Zhenfeng Jiang; Kevork Khadarian; Shan Yu; Yan Zhao; Chuncheng Xie; Kelvin Zhang; Minwei Zhu; Hong Shen; Zhiguo Lin; Chuanlu Jiang; Jia Shen; Yongri Zheng

doi:10.1016/j.canlet.2015.02.003

miR-603 promotes glioma cell growth via Wnt/β-catenin pathway by inhibiting WIF1 and CTNNBIP1

Cancer Lett. 2015 Apr 28;360(1):76-86. doi: 10.1016/j.canlet.2015.02.003. Epub 2015 Feb 10.

Authors

Mian Guo¹, Xiaoming Zhang¹, Guangzhi Wang², Jiahang Sun¹, Zhenfeng Jiang³, Kevork Khadarian⁴, Shan Yu⁵, Yan Zhao¹, Chuncheng Xie³, Kelvin Zhang⁶, Minwei Zhu³, Hong Shen³, Zhiguo Lin³, Chuanlu Jiang¹, Jia Shen⁷, Yongri Zheng⁸

Affiliations

¹ Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
² Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China; Department of Medical Service Management, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
³ Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
⁴ Dental School, University of California, Los Angeles, Los Angeles, CA 90095, USA.
⁵ Department of Pathology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.
⁶ Department of Biological Chemistry, Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095, USA.
⁷ Dental School, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: shenj02@gmail.com.
⁸ Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China. Electronic address: zhengyongrihyd@163.com.

PMID: 25681036
DOI: 10.1016/j.canlet.2015.02.003

Abstract

Gliomas are the most common and deadly type of brain tumor. In spite of progressive treatments, patient prognosis has not improved significantly. MicroRNAs are considered promising candidates for glioma therapy. MiR-603 was found overexpressed in both glioma tissues and cell lines. MiR-603 promoted cell proliferation, cell cycle progression and neurosphere formation. Conversely, inhibition of miR-603 remarkably reduced these effects. We confirmed that WIF1 and CTNNBIP1 are bona fide targets of miR-603. The negative correlation between miR-603 and these molecules' expression was shown by Pearson correlation in 50 primary glioma tissue samples. Furthermore, overexpression of miR-603 promoted nuclear β-catenin levels and TOPflash luciferase activity, indicating that miR-603 activates the Wnt/β-catenin signaling pathway. Our in vivo results confirmed the positive role of miR-603 in glioma development. We demonstrate that miR-603 regulates glioma development via its WIF1 and CTNNBIP1 targets, which suggests that miR-603 may be a promising candidate for therapeutic applications in glioma treatment.

Keywords: CTNNBIP1; Glioma; WIF1; Wnt/β-catenin; miR-603.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Animals
Brain Neoplasms / genetics
Brain Neoplasms / metabolism*
Brain Neoplasms / pathology
Cell Line, Tumor
Cell Proliferation*
Gene Expression Regulation, Neoplastic
Glioblastoma / genetics
Glioblastoma / metabolism*
Glioblastoma / pathology
Humans
Intracellular Signaling Peptides and Proteins / genetics
Intracellular Signaling Peptides and Proteins / metabolism*
Male
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics
MicroRNAs / metabolism*
RNA Interference
Repressor Proteins / genetics
Repressor Proteins / metabolism*
Time Factors
Transfection
Tumor Burden
Wnt Signaling Pathway*
beta Catenin / metabolism*

Substances

Adaptor Proteins, Signal Transducing
CTNNB1 protein, human
CTNNBIP1 protein, human
Intracellular Signaling Peptides and Proteins
MIRN603 microRNA, human
MicroRNAs
Repressor Proteins
WIF1 protein, human
beta Catenin