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PMID:23383034

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Citation

Jia, Z, Wang, K, Wang, G, Zhang, A and Pu, P (2013) MiR-30a-5p antisense oligonucleotide suppresses glioma cell growth by targeting SEPT7. PLoS ONE 8:e55008

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by targeting the mRNAs of hundreds of human genes. Variations in miRNA expression levels were shown to be associated with glioma. We have previously found miR-30a-5p overexpression in glioma cell lines and specimens. Bioinformatics analyses predict that several miRNAs, including miR-30a-5p, are involved in the post-transcriptional regulation of SEPT7. SEPT7 is a member of the septin family, which is a highly conserved subfamily of GTPases implicated in exocytosis, apoptosis, synaptogenesis, neurodegeneration and tumorigenesis. Our previous study has also demonstrated that SEPT7 expression is decreased in astrocytic gliomas with different grades and plays a tumor suppressor role. In the present study, we knocked down miR-30a-5p with antisense oligonucleotide (miR-30a-5p AS) in LN229 and SNB19 glioblastoma(GBM) cells, and found that cell growth and invasion were inhibited, while apoptosis was induced. miR-30a-5p AS treated cells showed upregulation of SEPT7 and downregulation of PCNA, cyclin D1, Bcl2, MMP2 and MMP9. In contrast, when miR-30a-5p mimics were transfected into LN229 and SNB19 GBM cells, cell growth and invasion were promoted and the expression of relevant proteins increased. Meanwhile, the effect of miR-30a-5p mimics on glioma cells can be reversed by transfection of SEPT7 construct. Additionaly, miR-30a-5p directly targeting SEPT7 was identified by the reporter gene assay. Our study demonstrates,for the first time, that miR-30a-5p is a bona fide negative regulator of SEPT7 and the oncogenic activity of miR-30a-5p in human gliomas is at least in part through the repression of SEPT7.

Links

PubMed PMC3557229 Online version:10.1371/journal.pone.0055008

Keywords

Adenoviridae/genetics; Apoptosis/genetics; Base Sequence; Cell Cycle Proteins/deficiency; Cell Cycle Proteins/genetics; Cell Line, Tumor; Cell Proliferation; G1 Phase Cell Cycle Checkpoints/genetics; Gene Expression Regulation, Neoplastic/genetics; Gene Knockdown Techniques; Glioma/pathology; Humans; MicroRNAs/genetics; Neoplasm Invasiveness; Oligonucleotides, Antisense/genetics; Resting Phase, Cell Cycle/genetics; Septins/deficiency; Septins/genetics; Transfection; Up-Regulation/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SEPT7

involved_in

GO:0030336: negative regulation of cell migration

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SEPT7

involved_in

GO:2000134: negative regulation of G1/S transition of mitotic cell cycle

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SEPT7

involved_in

GO:0043065: positive regulation of apoptotic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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