IGF2 mRNA binding protein 3 (IMP3) promotes glioma cell migration by enhancing the translation of RELA/p65

Bhargava, Shruti and Visvanathan, Abhirami and Patil, Vikas and Kumar, Anuj and Kesari, Santosh and Das, Saumitra and Hegde, Alangar S and Arivazhagan, Arimappamagan and Santosh, Vani and Somasundaram, Kumaravel (2017) IGF2 mRNA binding protein 3 (IMP3) promotes glioma cell migration by enhancing the translation of RELA/p65. In: ONCOTARGET, 8 (25). pp. 40469-40485.

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Abstract

The diffusely infiltrative nature of glioblastoma (GBM) makes them highly recurrent. IGF2 mRNA-binding protein 3 (IMP3), a GBM upregulated RNA binding protein, promotes glioma cell migration. An integrative bioinformatics analysis identified p65 (RELA), a subunit of NF-kappa B heterodimer as a target and an important mediator of IMP3 promoted glioma cell migration. IMP3 increased p65 protein levels without any change in p65 transcript levels, but promoted its polysome association. RIP-PCR demonstrated the binding of IMP3 to p65 transcript. UV crosslinking experiments with in vitro transcribed RNA confirmed the specific and direct binding of IMP3 to sites on p65 3'UTR. Further, IMP3 induced luciferase activity from p65 3'UTR reporter carrying wild type sites but not mutated sites. Exogenous overexpression of p65 from a 3'UTR-less construct rescued the reduced migration of glioma cells in IMP3 silenced condition. In addition, IMP3 silencing inhibited glioma stem-like cell maintenance and migration. The exogenous overexpression of 3'UTR-less p65 significantly alleviated the inhibition of neurosphere formation observed in IMP3 silenced glioma stem-like cells. Further, we show that IMP3 is transcriptionally activated by NF-kappa B pathway indicating the presence of a positive feedback loop between IMP3 and p65. This study establishes p65 as a novel target of IMP3 in increasing glioma cell migration and underscores the significance of IMP3-p65 feedback loop for therapeutic targeting in GBM.

Item Type:	Journal Article
Publication:	ONCOTARGET
Additional Information:	Copy right for this article belongs to the IMPACT JOURNALS LLC, 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	22 Jul 2017 05:33
Last Modified:	22 Jul 2017 05:33
URI:	http://eprints.iisc.ac.in/id/eprint/57459

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