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Volume 23
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10.3390/ijms23147741
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Article

Coexpression of TRPML1 and TRPML2 Mucolipin Channels Affects the Survival of Glioblastoma Patients

by
Giorgio Santoni
1,*,
Federica Maggi
2,
Consuelo Amantini
2,
Antonietta Arcella
3,
Oliviero Marinelli
1,
Massimo Nabissi
1,
Matteo Santoni
4 and
Maria Beatrice Morelli
1
1
School of Pharmacy, University of Camerino, 62032 Camerino, Italy
2
School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy
3
Neuropathology Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico Neuromed, 86077 Pozzilli, Italy
4
Medical Oncology Unit, Hospital of Macerata, 62100 Macerata, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(14), 7741; https://doi.org/10.3390/ijms23147741
Submission received: 10 March 2022 / Revised: 5 July 2022 / Accepted: 11 July 2022 / Published: 13 July 2022
(This article belongs to the Special Issue Glioblastoma: Recapitulating the Key Breakthroughs and Future Perspective)
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Abstract

Among brain cancers, glioblastoma (GBM) is the most malignant glioma with an extremely poor prognosis. It is characterized by high cell heterogeneity, which can be linked to its high malignancy. We have previously demonstrated that TRPML1 channels affect the OS of GBM patients. Herein, by RT-PCR, FACS and Western blot, we demonstrated that TRPML1 and TRPML2 channels are differently expressed in GBM patients and cell lines. Moreover, these channels partially colocalized in ER and lysosomal compartments in GBM cell lines, as evaluated by confocal analysis. Interestingly, the silencing of TRPML1 or TRPML2 by RNA interference results in the decrease in the other receptor at protein level. Moreover, the double knockdown of TRPML1 and TRPML2 leads to increased GBM cell survival with respect to single-channel-silenced cells, and improves migration and invasion ability of U251 cells. Finally, the Kaplan–Meier survival analysis demonstrated that patients with high TRPML2 expression in absence of TRPML1 expression strongly correlates with short OS, whereas high TRPML1 associated with low TRPML2 mRNA expression correlates with longer OS in GBM patients. The worst OS in GBM patients is associated with the loss of both TRPML1 and TRPML2 channels.
Keywords: glioblastoma; heterogeneity; mucolipin channels; overall survival glioblastoma; heterogeneity; mucolipin channels; overall survival

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MDPI and ACS Style

Santoni, G.; Maggi, F.; Amantini, C.; Arcella, A.; Marinelli, O.; Nabissi, M.; Santoni, M.; Morelli, M.B. Coexpression of TRPML1 and TRPML2 Mucolipin Channels Affects the Survival of Glioblastoma Patients. Int. J. Mol. Sci. 2022, 23, 7741. https://doi.org/10.3390/ijms23147741

AMA Style

Santoni G, Maggi F, Amantini C, Arcella A, Marinelli O, Nabissi M, Santoni M, Morelli MB. Coexpression of TRPML1 and TRPML2 Mucolipin Channels Affects the Survival of Glioblastoma Patients. International Journal of Molecular Sciences. 2022; 23(14):7741. https://doi.org/10.3390/ijms23147741

Chicago/Turabian Style

Santoni, Giorgio, Federica Maggi, Consuelo Amantini, Antonietta Arcella, Oliviero Marinelli, Massimo Nabissi, Matteo Santoni, and Maria Beatrice Morelli. 2022. "Coexpression of TRPML1 and TRPML2 Mucolipin Channels Affects the Survival of Glioblastoma Patients" International Journal of Molecular Sciences 23, no. 14: 7741. https://doi.org/10.3390/ijms23147741

APA Style

Santoni, G., Maggi, F., Amantini, C., Arcella, A., Marinelli, O., Nabissi, M., Santoni, M., & Morelli, M. B. (2022). Coexpression of TRPML1 and TRPML2 Mucolipin Channels Affects the Survival of Glioblastoma Patients. International Journal of Molecular Sciences, 23(14), 7741. https://doi.org/10.3390/ijms23147741

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