MicroRNA-7 directly targets insulin-like growth factor 1 receptor to inhibit cellular growth and glucose metabolism in gliomas.
BACKGROUND
Recent studies observed that altered energy metabolism has become widespread in cancer cells along with other cancer-associated traits that have been accepted as hallmarks of cancer. Akt signaling pathway is involved in the aerobic glycolysis program. However, mechanisms underlying the regulation of aerobic glycolysis and Akt activity in gliomas remain unclear. MicroRNAs are a group of small non-coding RNAs that can function as endogenous RNA interference to regulate expression of targeted genes. This study was conducted to detect the function of miR-7 targeting insulin-like growth factor 1 receptor (IGF-1R), which is an upstream regulator of Akt.


METHODS
MicroRNA expression data for gliomas and normal controls were downloaded from The Cancer Genome Atlas (TCGA) database. Quantitative real-time PCR was used to measure the microRNA-7 (miR-7) expression level, and Western blot was performed to detect protein expression in U87 and U251 cells. Colony formation assay and glycolysis stress test were also conducted. Luciferase reporter assay was used to identify the mechanism of IGF-1R and miR-7 regulation.


RESULTS
miR-7 was downregulated in human glioma tissues based on TCGA database. Forced expression of miR-7 or IGF-1R knockdown inhibited colony formation and glucose metabolic capabilities of glioma cells in vitro and decreased the p-Akt expression level. Bioinformatics analysis results indicated that IGF-1R could be a target of miR-7. Western blot and luciferase reporter assays showed that miR-7 modulated IGF-1R expression by directly targeting the binding site within the 3'-untranslated region.


CONCLUSIONS
This study provides the first evidence that miR-7 inhibits cellular growth and glucose metabolism in gliomas, at least partially, by regulating the IGF-1R/Akt signaling pathway. Therefore, miR-7 is a promising molecular drug for glioma treatment.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_211.
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. wangboxuzhou@126.com.
Bo
B
Wang
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. sufei1981@126.com.
Fei
F
Sun
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. dongyutianqi@126.com.
Nan
N
Dong
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. szgxuzhou@163.com.
Zhenguo
Z
Sun
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. hanyutianqi@163.com.
Yi
Y
Diao
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. zc2015@yeah.net.
Cheng
C
Zheng
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. sunjianxin2015@126.com.
Jianxin
J
Sun
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. yangyangxuzhou@yeah.net.
Yang
Y
Yang
Department of Neurosurgery, Xuzhou Central Hospital, Xuzhou, 221009, China. jingdehua1963@163.com.
Dehua
D
Jiang
D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019295:Computational Biology; D030541:Databases, Genetic; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D005947:Glucose; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin; C000597236:IGF1R protein, human; C549242:MIRN7-1 microRNA, human