Rani , S.B. and Rathod , S.S. and Karthik, S. and Kaur , N. and Muzumdar , D. and Shiras , A.S. (2013) MiR-145 functions as a tumor-suppressive RNA by targeting Sox9 and adducin 3 in human glioma cells. Neuro-Oncology, 15 (10). pp. 1302-1316.

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Abstract

Background. MicroRNAs (miRNAs) are increasingly being recognized as being involved in cancer development and progression in gliomas. Methods. Using a model cell system developed in our lab to study glioma progression comprising human neuroglial culture (HNGC)–1 and HNGC-2 cells, we report here that miR-145 is one of the miRNAs significantly downregulated during malignant transformation in glioblastoma multiforme (GBM). In a study using tumor samples derived from various glioma grades, we show that expression of miR-145 is decreased in a graded manner, with GBM patients showing lowest expression relative to lower-grade gliomas (P , .05) and normal brain tissues (P , .0001). Functional studies involving ectopic expression of miR-145 in glioma cells had a negative impact on cell proliferation and tumor development, as well as invasion and induced apoptosis, providing further support to the concept that inactivation of miR-145 is important for glioma disease pathogenesis. More notably, these growth-suppressive effects of miR-145 are mediated through its target proteins Sox9 and the cell adhesionassociated molecule adducin 3 (ADD3). Results. Inhibiting Sox9 and ADD3 rescued effects of miR-145 loss. Interestingly, miR-145 loss in glioma cells led to overexpression of molecules involved in cell proliferation, like cyclin D1, c-myc, and N-myc, as well as enhanced expression of cell adhesion- and invasion-related molecules N-cadherin and E-cadherin, an effect which was again restored upon miR-145 overexpression in glioma cells. The miR-145 promoter was methylated at its cytosine–phosphate–guanine (CpG) islands in the glioma cell lines studied. Conclusion. Our study demonstrates that miR-145 has a tumor-suppressive function in glioblastoma in that it reduces proliferation, adhesion, and invasion of glioblastomacells, apparently by suppressing the activityof oncogenic proteins Sox9 and ADD3. Reduced levels of miR-145 may lead to neoplastic transformation and malignant progression in glioma due to unregulated activity of these proteins.

Item Type:	Article
Additional Information:	This is Open Access article (for full text click above web link)
Subjects:	Cancer Biology
Depositing User:	Mr. Rameshwar Nema
Date Deposited:	13 Apr 2015 09:34
Last Modified:	03 Jul 2015 05:57
URI:	http://nccs.sciencecentral.in/id/eprint/66

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