MiR-30a-5p Antisense Oligonucleotide Suppresses Glioma Cell Growth by Targeting SEPT7

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.

MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

“…On the contrary, miR-30a-5p is overexpressed in glioma tissues and cell lines when compared with normal brain tissues, and its level of expression is positively associated with tumor grade of malignancy (11). Additionally, inhibition of miR-30a-5p by using the antisense oligonucleotide suppresses glioma cell growth via upregulation of SEPT7, which is downregulated in glioma (20). These studies suggest that miR-30a-5p has a dual role in cancer progression depending on the type of cancer.…”

SEPT7 (septin 7)

“…This particular study gives evidence that SEPT7 is primarily involved in gliomagenesis and leads to suppression of glioma cell growth , Xu et al, 2010. SEPT7 is targeted by MiR30a-5p to cause glioma cell growth (Jia et al, 2013).…”

“…There are already cytoplasmic, nuclear, and overall (total) SEPT7 protein expression levels which have also been determined in PTC (Igci et al, 2014). SEPT7 was also shown to be negatively regulated by miR-30a-5p in glioma cells (Jia et al, 2013). There is very high expression of SEPT7 proteins in cerebral cortex but moderate expression in hippocampus, lateral ventricle and cerebellum of CNS.…”

MicroRNA‑30a suppresses non‑small‑cell lung cancer by targeting Myb‑related protein B

“…Various genetic and epigenetic alternations occur during NSCLC tumorigenesis; therefore, to pursue more efficient therapeutic strategies, contemporary studies are focusing on the molecular mechanisms underlying the genetic and epigenetic processes involved in NSCLC (21)(22)(23). miR-30 family has provided insight into the prevention, diagnosis and treatment of human diseases (24)(25)(26). In a previous study, it was demonstrated that miR-155 downregulation was able to induce cell apoptosis and cell cycle arrest by targeting various anti-apoptotic factors (27).…”

“…It has been demonstrated that miR-30a-5p expression is upregulated in glioma cell lines and glioma specimens (33). Knockdown of miR-30a-5p with antisense oligonucleotide in LN229 and SNB19 glioblastoma (GBM) cells inhibited cell growth and invasion, and induced apoptosis (34). 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 (34).…”