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miR-217–casein kinase-2 cross talk regulates ERK activation in ganglioglioma

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Abstract

Gangliogliomas (GGs) are the most commonly diagnosed long-term epilepsy-associated tumors (LEATs). Although molecular characterizations of brain tumors have identified few novel biomarkers among the LEATs, mechanisms of pathogenesis remain poorly understood. In this study, global microarray-based microRNA (miRNA) expression profile on a set of 9 GGs indicated 66 miRNAs to be differentially expressed in GG as compared to normal brain. The differences validated by qRT-PCR indicated microRNA-217 to be the most downregulated. Through insilico analysis, ERK1/2 and casein kinase (CK-2α) were predicted to be miR-217 regulated. As decreased miR-217 expression was concomitant with upregulated ERK1/2 and CK-2α levels in GG; the interplay between these molecules was investigated in primary human neural precursor cells to mimic the glioneuronal characteristics of these tumors. miR-217 over-expression-mediated decrease in pERK, CK-2α, and mGluR1 levels was accompanied with increase in glycogen accumulation. Importantly, increase in miR-217 levels upon CK-2α inhibition indicated inverse correlation between the two. Inhibition of CK-2α also decreased ERK and mGluR1 levels. By demonstrating, for the first time, the existence of miR-217–CK-2 cross talk and its effects on known epileptogenic factors, these findings provide a unique insight into the pathogenesis of ganglioglioma. By highlighting the role of CK-2 in affecting miR-217/ERK/mGluR1 interplay, this study suggests that targeting CK-2 may afford a novel strategy aimed at LEATs.

Key messages

  • Global microarray of ganglioglioma indicates downregulation of miR-217.

  • Decreased miR-217 expression is concomitant with elevated CK-2α and Erk levels.

  • Inverse correlation between miR-217 and CK-2α in primary human neural precursors.

  • miR-217 agomir or CK-2α inhibition decreases pERK and mGluR1 levels.

  • CK-2α affects miR-217/ERK/mGluR1 interplay in long-term epilepsy-associated tumors.

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Acknowledgements

The work was supported by a research grant from the Department of Biotechnology (DBT, Government of India #BT/Med/30/SP11016/2015) to ES, and intramural fund (A.I.I.M.S) to VT and CS. FA is supported by a research fellowship from DBT, Government of India. The technical assistance of Rajesh Kumar Kumawat is acknowledged.

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Authors and Affiliations

  1. All India Institute of Medical Sciences, New Delhi, 110029, India

    Atreye Majumdar, Pankaj Pathak, Vivek Tandon, Manjari Tripathi, P. Saratchandra & Chitra Sarkar

  2. National Brain Research Centre, Nainwal Mode, NH-8, Manesar, Gurgaon, Haryana, 122051, India

    Fahim Ahmad, Touseef Sheikh, Reshma Bhagat, Shanker Datt Joshi, Pankaj Seth & Ellora Sen

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  1. Atreye Majumdar
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Atreye Majumdar and Fahim Ahmad are equal contributors.

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Majumdar, A., Ahmad, F., Sheikh, T. et al. miR-217–casein kinase-2 cross talk regulates ERK activation in ganglioglioma. J Mol Med 95, 1215–1226 (2017). https://doi.org/10.1007/s00109-017-1571-z

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  • DOI: https://doi.org/10.1007/s00109-017-1571-z

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