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

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, FA...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2022-07, Vol.23 (14), p.7741
Main Authors: Santoni, Giorgio, Maggi, Federica, Amantini, Consuelo, Arcella, Antonietta, Marinelli, Oliviero, Nabissi, Massimo, Santoni, Matteo, Morelli, Maria Beatrice
Format: Article
Language:English
Subjects:
Biopsy
Bladder cancer
Brain cancer
Breast cancer
Cell lines
Channels
DNA methylation
Flow cytometry
Gene expression
Glioblastoma
Glioma
Heterogeneity
Localization
Malignancy
Medical prognosis
mucolipin channels
Mutation
overall survival
Prostate cancer
Protein expression
Proteins
RNA-mediated interference
Survival
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23147741