MicroRNA-542-3p Suppresses Tumor Cell Invasion via Targeting AKT Pathway in Human Astrocytoma.
The molecular mechanism underlying constitutive activation of AKT signaling, which plays essential roles in astrocytoma progression, is not fully characterized. Increasing numbers of studies have reported that microRNAs are involved in the malignant behavior of astrocytoma cells via directly targeting multiple oncogenes or tumor suppressors. Here, we found that microRNA (miR)-542-3p expression was decreased in glioblastoma cell lines and astrocytoma tissues, and reduced levels of miR-542-3p expression correlated with high histopathological grades and poor prognosis of astrocytoma patients. Exogenous miR-542-3p suppressed glioblastoma cell invasion through not only targeting AKT1 itself but also directly down-regulating its two important upstream regulators, namely, integrin-linked kinase and PIK3R1. Notably, overexpressing miR-542-3p decreased AKT1 phosphorylation and directly and indirectly repressed nuclear translocation and transactivation activity of β-catenin to exert its anti-invasive effect. Furthermore, the miR-542-3p expression level negatively correlated with AKT activity as well as levels of integrin-linked kinase and PIK3R1 in human astrocytoma specimens. These findings suggest that miR-542-3p acts as a negative regulator in astrocytoma progression and that miR-542-3p down-regulation contributes to aberrant activation of AKT signaling, leaving open the possibility that miR-542-3p may be a potential therapeutic target for high grade astrocytoma.
From the Departments of Microbiology and the Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, and.
Junchao
J
Cai
the Departments of Cardiology and.
JingJing
J
Zhao
Neurosurgery and.
Nu
N
Zhang
From the Departments of Microbiology and the Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, and.
Xiaonan
X
Xu
From the Departments of Microbiology and the Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, and.
Rong
R
Li
Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University.
Yang
Y
Yi
From the Departments of Microbiology and the Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, and.
Lishan
L
Fang
From the Departments of Microbiology and the Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, and.
Le
L
Zhang
From the Departments of Microbiology and the Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, and.
Mengfeng
M
Li
the Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, and wujh@mail.sysu.edu.cn.
Jueheng
J
Wu
Neurosurgery Intensive Care Unit, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong 510080, China hengzi00@gmail.com.
Heng
H
Zhang
D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D058543:Class Ia Phosphatidylinositol 3-Kinase; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005909:Glioblastoma / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism; D000099200:Scaffold Protein ILK
D020413:3' Untranslated Regions; D058543:Class Ia Phosphatidylinositol 3-Kinase; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D051176:beta Catenin; D000099200:Scaffold Protein ILK; C572357:MIRN542 microRNA, human; C588001:PIK3R1 protein, human; C494918:AKT1 protein, human
AKT signaling; Akt PKB; astrocytoma; cancer biology; cell invasion; invasiveness; microRNA-542-3p; neurobiology; signal transduction; β-catenin