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miR-218 inhibits the migration and invasion of glioma U87 cells through the Slit2-Robo1 pathway.

Gu JJ, Gao GZ, Zhang SM - Oncol Lett (2015)

Bottom Line: Malignant gliomas are the most common primary brain tumors in adults and are associated with the highest mortality rate.Preventing the invasive behavior of malignant glioma cells by altering effector molecules can significantly improve the prognosis of a patient. microRNAs (miRNAs) are small noncoding RNAs, ~22 nucleotides in length, that are able to function as oncogenes or tumor suppressors in human cancer.In addition, it was demonstrated that miR-218 inactivated the Slit2-Robo1 pathway through downregulating Robo1 expression by directly targeting the 3'-untranslated region (3'-UTR) of Robo1.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China.

ABSTRACT

Malignant gliomas are the most common primary brain tumors in adults and are associated with the highest mortality rate. Glioma invasion is one of the most notable causes of the poor prognosis of this cancer. Preventing the invasive behavior of malignant glioma cells by altering effector molecules can significantly improve the prognosis of a patient. microRNAs (miRNAs) are small noncoding RNAs, ~22 nucleotides in length, that are able to function as oncogenes or tumor suppressors in human cancer. In the present study, the expression level of miRNA 218 (miR-218) was found to be markedly downregulated in glioma cell lines and human primary glioma tissues. miR-218 upregulation was found to dramatically reduce the migratory speed and invasive ability of glioma cells. Furthermore, it was demonstrated that ectopic expression of miR-218 in glioma cells resulted in the downregulation of roundabout, axon guidance receptor, homolog 1 (Robo1), upregulation of Slit homolog 2 (Slit2) and the expression of associated proteins following Robo1 knockdown by small interfering RNA. In addition, it was demonstrated that miR-218 inactivated the Slit2-Robo1 pathway through downregulating Robo1 expression by directly targeting the 3'-untranslated region (3'-UTR) of Robo1. The present results indicate that miR-218 plays important roles in preventing the invasiveness of glioma cells, and reveals a novel mechanism of miRNA-mediated direct suppression of the Slit2-Robo1 pathway in glioma.

No MeSH data available.


Related in: MedlinePlus

Upregulation of miR-218 reduces Robo1 expression through the inactivation of Slit2-Robo1 signaling. (A and B) The U87 cells were treated with control, NC and miR-218 mimics, and the levels of Robo1 and Slit2 mRNA were measured by quantitative polymerase chain reaction.(C) The level of Robo1 and Slit2 protein expression in the U87 cells was measured by western blot analysis. *P<0. 05. Robo 1, roundabout, axon guidance receptor, homolog 1; Slit2, Slit homolog 2; NC, negative control; miR-218, microRNA 218.
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f3-ol-09-04-1561: Upregulation of miR-218 reduces Robo1 expression through the inactivation of Slit2-Robo1 signaling. (A and B) The U87 cells were treated with control, NC and miR-218 mimics, and the levels of Robo1 and Slit2 mRNA were measured by quantitative polymerase chain reaction.(C) The level of Robo1 and Slit2 protein expression in the U87 cells was measured by western blot analysis. *P<0. 05. Robo 1, roundabout, axon guidance receptor, homolog 1; Slit2, Slit homolog 2; NC, negative control; miR-218, microRNA 218.

Mentions: Development of invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Numerous studies have reported that the Slit2-Robo1 signaling channels can inhibit glioma invasion and migration. However, the specific roles of Slit2/Robo1 in cancer cell invasion have not yet been completely elucidated in vivo. The present study also observed, using qPCR and western blot analysis, that treatment with the miR-218 mimic for 24 h significantly upregulated the expression of Slit2, which was followed by a decrease in Robo1 (Fig. 3). These results indicate that miR-218 reduced the expression of Robo1 via the inactivation of Slit2-Robo1 signaling.


miR-218 inhibits the migration and invasion of glioma U87 cells through the Slit2-Robo1 pathway.

Gu JJ, Gao GZ, Zhang SM - Oncol Lett (2015)

Upregulation of miR-218 reduces Robo1 expression through the inactivation of Slit2-Robo1 signaling. (A and B) The U87 cells were treated with control, NC and miR-218 mimics, and the levels of Robo1 and Slit2 mRNA were measured by quantitative polymerase chain reaction.(C) The level of Robo1 and Slit2 protein expression in the U87 cells was measured by western blot analysis. *P<0. 05. Robo 1, roundabout, axon guidance receptor, homolog 1; Slit2, Slit homolog 2; NC, negative control; miR-218, microRNA 218.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356403&req=5

f3-ol-09-04-1561: Upregulation of miR-218 reduces Robo1 expression through the inactivation of Slit2-Robo1 signaling. (A and B) The U87 cells were treated with control, NC and miR-218 mimics, and the levels of Robo1 and Slit2 mRNA were measured by quantitative polymerase chain reaction.(C) The level of Robo1 and Slit2 protein expression in the U87 cells was measured by western blot analysis. *P<0. 05. Robo 1, roundabout, axon guidance receptor, homolog 1; Slit2, Slit homolog 2; NC, negative control; miR-218, microRNA 218.
Mentions: Development of invasiveness by malignant glioma cells involves multiple genetic alterations in signaling pathways. Numerous studies have reported that the Slit2-Robo1 signaling channels can inhibit glioma invasion and migration. However, the specific roles of Slit2/Robo1 in cancer cell invasion have not yet been completely elucidated in vivo. The present study also observed, using qPCR and western blot analysis, that treatment with the miR-218 mimic for 24 h significantly upregulated the expression of Slit2, which was followed by a decrease in Robo1 (Fig. 3). These results indicate that miR-218 reduced the expression of Robo1 via the inactivation of Slit2-Robo1 signaling.

Bottom Line: Malignant gliomas are the most common primary brain tumors in adults and are associated with the highest mortality rate.Preventing the invasive behavior of malignant glioma cells by altering effector molecules can significantly improve the prognosis of a patient. microRNAs (miRNAs) are small noncoding RNAs, ~22 nucleotides in length, that are able to function as oncogenes or tumor suppressors in human cancer.In addition, it was demonstrated that miR-218 inactivated the Slit2-Robo1 pathway through downregulating Robo1 expression by directly targeting the 3'-untranslated region (3'-UTR) of Robo1.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China.

ABSTRACT

Malignant gliomas are the most common primary brain tumors in adults and are associated with the highest mortality rate. Glioma invasion is one of the most notable causes of the poor prognosis of this cancer. Preventing the invasive behavior of malignant glioma cells by altering effector molecules can significantly improve the prognosis of a patient. microRNAs (miRNAs) are small noncoding RNAs, ~22 nucleotides in length, that are able to function as oncogenes or tumor suppressors in human cancer. In the present study, the expression level of miRNA 218 (miR-218) was found to be markedly downregulated in glioma cell lines and human primary glioma tissues. miR-218 upregulation was found to dramatically reduce the migratory speed and invasive ability of glioma cells. Furthermore, it was demonstrated that ectopic expression of miR-218 in glioma cells resulted in the downregulation of roundabout, axon guidance receptor, homolog 1 (Robo1), upregulation of Slit homolog 2 (Slit2) and the expression of associated proteins following Robo1 knockdown by small interfering RNA. In addition, it was demonstrated that miR-218 inactivated the Slit2-Robo1 pathway through downregulating Robo1 expression by directly targeting the 3'-untranslated region (3'-UTR) of Robo1. The present results indicate that miR-218 plays important roles in preventing the invasiveness of glioma cells, and reveals a novel mechanism of miRNA-mediated direct suppression of the Slit2-Robo1 pathway in glioma.

No MeSH data available.


Related in: MedlinePlus