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Implication of connexin30 on the stemness of glioma: connexin30 reverses the malignant phenotype of glioma by modulating IGF-1R, CD133 and cMyc

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A Correction to this article was published on 24 March 2021

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Abstract

Gap-junctional intercellular communication (GJIC) plays a major role in the malignant growth of glioma. Although the mechanistic aspects of GJIC have been extensively studied, the role of connexins in the regulation of the malignant behavior of glioma stem cells (GSCs) remains unclear. In our previous studies, we have shown that connexin30 can interfere with the insulin-like growth factor 1 receptor (IGF-1R), which is known for self-renewal and pluripotency. Following our earlier in vitro observation, in this work, we aimed to study the consequence of this influence of Cx30 on IGF-1R by evaluating the marker of GSCs, CD133 and oncoprotein, cMyc. We strengthened our basis by examining human glioma samples of different grades as well as rat C6 xenografts (Cx30-transfected and -non-transfected C6 cells) along with the sphere formation assays in vitro. Investigation of stemness-related CD133 and cMyc in human samples and rat xenografts exhibited a reciprocal relationship between Cx30 and IGF-1R in the low and high grades (HG) of glioma. Cx30 was completely abolished in HG; levels of IGF-1R, CD133 and cMyc expression were positively correlated with HG. Cx30 transfection could attenuate the malignant burden of glioma in rat xenografts. Cx30 transfection also altered the tumor sphere formation of C6 glioma cells in vitro, an important property of GSCs, and there was a significant reduction of CD133 and cMyc expression by Cx30 both in vitro and in vivo. These factors indicate that dysfunction of Cx30 plays a crucial role in the prevention of the stemness of glioma, and the exploitation of this feature will help in the management of glioma.

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Acknowledgements

We gratefully acknowledge the financial support from the Indian Council of Medical Research (No. 52/2/2008-BMS, Dated: 25.03.2010), Department of Science and Technology (No. SR/FT/LS-140/2008), and the University Grant Commission-Basic Scientific Research Research (No. GCCO/A-2/UGC-MERITORIOUS/2013/14, Dated: 10.05.2013). The authors also thank Mr. P.P. Elango for the language editing of the entire manuscript.

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  1. Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu, 600 025, India

    Sankaradoss Arun & Arambakkam Janardhanam Vanisree

  2. Department of Neuropathology, Tamil Nadu Multi-Specialty Hospital, Chennai, Tamil Nadu, 600 003, India

    Shantha Ravisankar

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  1. Sankaradoss Arun
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Correspondence to Arambakkam Janardhanam Vanisree.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Human Ethics Committee of the Government General Hospital, Madras Medical College, Chennai, Tamil Nadu and India. Institutional guidelines for the care and use of animals were also followed.

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Arun, S., Ravisankar, S. & Vanisree, A.J. Implication of connexin30 on the stemness of glioma: connexin30 reverses the malignant phenotype of glioma by modulating IGF-1R, CD133 and cMyc. J Neurooncol 135, 473–485 (2017). https://doi.org/10.1007/s11060-017-2608-4

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  • DOI: https://doi.org/10.1007/s11060-017-2608-4

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