MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation

被引：28

作者：

Conti, Alfredo ^{[1
]}

Romeo, Sara G. ^{[1
]}

Cama, Annamaria ^{[1
]}

La Torre, Domenico ^{[1
]}

Barresi, Valeria ^{[2
]}

Pezzino, Gaetana ^{[2
]}

Tomasello, Chiara ^{[2
]}

Cardali, Salvatore ^{[1
]}

Angileri, Filippo F. ^{[1
]}

Polito, Francesca ^{[3
]}

Ferlazzo, Guido ^{[2
]}

Di Giorgio, Rosamaria ^{[3
]}

Germano, Antonino ^{[1
]}

Aguennouz, M'hammed ^{[3
]}

机构：

[1] Univ Messina, Dept Biomed & Dent Sci & Morphofunct Imaging, Messina, Italy

[2] Univ Messina, Dept Adulthood & Childhood Pathol G Barresi, Messina, Italy

[3] Univ Messina, Dept Clin & Expt Med, Messina, Italy

来源：

TUMOR BIOLOGY | 2016年 / 37卷 / 10期

关键词：

miRNA microarray; miRNA-363; Gap-43; Astrocytoma; Glioblastoma multiforme; HIGH-GRADE GLIOMA; BRAIN-TUMORS; MICRORNAS; GLIOBLASTOMA; SIGNATURE; GROWTH; INVASIVENESS; PROGRESSION; INHIBITORS; PROGNOSIS;

D O I：

10.1007/s13277-016-5273-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The role of microRNAs (miRNAs) in glioma biology is increasingly recognized. To investigate the regulatory mechanisms governing the malignant signature of gliomas with different grades of malignancy, we analyzed miRNA expression profiles in human grade I-IV tumor samples and primary glioma cell cultures. Multiplex real-time PCR was used to profile miRNA expression in a set of World Health Organization (WHO) grade I (pilocytic astrocytoma), II (diffuse fibrillary astrocytoma), and IV (glioblastoma multiforme) astrocytic tumors and primary glioma cell cultures. Primary glioma cell cultures were used to evaluate the effect of transfection of specific miRNAs and miRNA inhibitors. miRNA microarray showed that a set of miRNAs was consistently upregulated in all glioma samples. miR-363 was upregulated in all tumor specimens and cell lines, and its expression correlated with tumor grading. The transfection of glioma cells with the specific inhibitor of miR-363 increased the expression level of tumor suppressor growth-associated protein 43 (GAP-43). Transfection of miR-363 induced cell survival, while inhibition of miR-363 significantly reduced glioma cell viability. Furthermore, miRNA-363 inhibition induced the downregulation of AKT, cyclin-D1, matrix metalloproteinase (MMP)-2, MMP-9, and Bcl-2 and upregulation of caspase 3. Together, these data suggest that the upregulation of miR-363 may play a role in malignant glioma signature.

引用

页码：14035 / 14048

页数：14

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