Transcriptional suppression of microRNA-27a contributes to laryngeal cancer differentiation via GSK-3β-involved Wnt/β-catenin pathway

被引：30

作者：

Chen, Sheng ^{[1
]}

Sun, Yuan-Yuan ^{[1
]}

Zhang, Zhao-Xiong ^{[1
]}

Li, Yun-Hui ^{[2
]}

Xu, Zhen-Ming ^{[3
]}

Fu, Wei-Neng ^{[1
]}

机构：

[1] China Med Univ, Dept Med Genet, Shenyang 110122, Peoples R China

[2] PLA, Dept Lab Med, Hosp 202, Shenyang 110003, Peoples R China

[3] PLA, Hosp 463, Dept Otolaryngol, Shenyang 110007, Peoples R China

来源：

ONCOTARGET | 2017年 / 8卷 / 09期

基金：

中国国家自然科学基金;

关键词：

laryngeal cancer; miR-27a; ATRA; differentiation; GSK-3; beta; STEM-LIKE CELLS; GASTRIC-CANCER; BREAST-CANCER; RAR-ALPHA; MIR-27A; GLIOBLASTOMA; ROLES;

D O I：

10.18632/oncotarget.14769

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

miR-27a regulates cell differentiation in a variety of diseases. However, whether and how miR-27a participates in laryngeal cancer cell differentiation remains unknown. Therefore, we explored role and molecular mechanism of miR-27a in laryngeal cancer differentiation in the study. We found that miR-27a expression was inversely correlated with laryngeal cancer differentiation degree based on the clinical pathological diagnosis of each patient. miR-27 asignificantly rescued differentiation and inhibited beta-catenin, LEF1, OCT4 and SOX2 in Wnt/beta-catenin pathway in all-transretinoic acid (ATRA)-induced laryngeal cancer cells. Bindings of RARa to miR-27a and miR-27a to GSK-3 beta were confirmed by ChIP and Luciferase reporter assays, respectively. In conclusion, miR-27a is a negative regulator in laryngeal cancer differentiation. RARa-mediated miR-27a transcriptional inactivation releases the inhibition of miR-27a on GSK-3 beta leading to laryngeal cancer differentiation through GSK-3 beta-involved Wnt/beta-catenin pathway, suggesting that miR-27a is a usefully therapeutic target at least in ATRA-induced laryngeal cancer differentiation.

引用

页码：14708 / 14718

页数：11

共 29 条

[1]

miR-27a and miR-214 exert opposite regulatory roles in Th17 differentiation via mediating different signaling pathways in peripheral blood CD4+ T lymphocytes of patients with relapsing-remitting multiple sclerosis [J].