MicroRNA-184 inhibits cell proliferation and invasion, and specifically targets TNFAIP2 in Glioma.

Abstract

BACKGROUND:

miRNA-184 is an oncogene in human hepatocellular carcinoma but acts as a tumor suppressor in tongue squamous cell carcinoma. Studies have shown that miR-184 was down-regulated in glioma and TNFα-induced protein 2 (TNFAIP2) was closely related to tumorigenesis. This study aimed to determine the functions of miR-184 in glioma and the mechanisms of miRNA-184-TNFAIP2 mediated glioma progression.

METHODS:

Real-time reverse-transcription PCR detected expression of miR-184 and TNFAIP2. U87 and U251 cells were transfected with miR-184 mimic, inhibitor, or negative control miRNA, and their invasion abilities were assayed. Cellular proliferation was measured by the cell counting kit-8 assay. miR-184 effects on glioma cell apoptosis and cell cycle were assessed by flow cytometer. Biological information software have predicted that miR-184 could target TNFα-induced protein 2 (TNFAIP2), Which was further validated by Western blot and qRT-PCR in glioma cells. In vivo, U87 cells transduced with either lentiviral over-expressed miR-184 or control lentivirus were injected into nude mice subcutaneously and intracranial respectively.

RESULTS:

Expression of miR-184 was significantly lower in glioma tissues and cell-lines compared to normal brain tissues. Protein and mRNA expression of TNFAIP2 were inversely correlated with miR-184 in glioma. In vitro, proliferation and invasion abilities were also decreased in U87 and U251 cells after transfection with miR-184 mimic. In vivo, the xenografted tumor size in the miR-184 overexpressing group were smaller than the miR-NC group. Concordantly, U87 and U251 cells transfected with miR-184 mimic had a higher apoptosis rate, triggering an accumulation of cells at the G0/G1 phase and decreased cells in S-phase.

CONCLUSIONS:

miR-184 could regulate TNFAIP2 expression and affected its translation in glioma. miR-184 could also inhibit glioma progression and might serve as a novel therapeutic target in glioma.

• Authors: Zhe Cheng, Hang Zhou Wang, Xuetao Li, Zhiwu Wu, Yong Han, Yanyan Li, Guilin Chen, Xueshun Xie, Yulun Huang, Ziwei Du, Youxin Zhou
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 34 Pg. 27 (Mar 26 2015) ISSN: 1756-9966 [Electronic] England
• PMID: 25888093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• MIRN184 microRNA, human
• MicroRNAs
• TNFAIP2 protein, human

Topics

• Adult
• Aged
• Animals
• Apoptosis (genetics)
• Brain Neoplasms (genetics, pathology)
• Cell Cycle (genetics)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation
• Cytokines (genetics)
• Disease Models, Animal
• Female
• Gene Expression Regulation, Neoplastic
• Glioma (genetics, pathology)
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• Neoplasm Grading
• Neoplasm Staging
• RNA Interference
• Xenograft Model Antitumor Assays