Targeting the Regulatory Subunit R2Alpha of Protein Kinase A in Human Glioblastoma through shRNA-Expressing Lentiviral Vectors

Viruses

Arianna Calistri¹  Cristina Parolin¹  Elisa Saccon¹  Giorgio Palù¹  Claudia Del Vecchio¹  Carla Mucignat-Caretta¹  Maira Zorzan¹  Stefania Vogiatzis¹ 

[1] Department of Molecular Medicine, University of Padova, Via Gabelli 63, 35121 Padova, Italy;

关键词: lentiviral vectors;    glioblastoma;    protein kinase A;    brain tumor;    short hairpin RNA;    cAMP;   

DOI  :  10.3390/v13071361

来源: DOAJ

【 摘 要 】

Glioblastoma is the most malignant and most common form of brain tumor, still today associated with a poor 14-months median survival from diagnosis. Protein kinase A, particularly its regulatory subunit R2Alpha, presents a typical intracellular distribution in glioblastoma cells compared to the healthy brain parenchyma and this peculiarity might be exploited in a therapeutic setting. In the present study, a third-generation lentiviral system for delivery of shRNA targeting the regulatory subunit R2Alpha of protein kinase A was developed. Generated lentiviral vectors are able to induce an efficient and stable downregulation of R2Alpha in different cellular models, including non-stem and stem-like glioblastoma cells. In addition, our data suggest a potential correlation between silencing of the regulatory subunit of protein kinase A and reduced viability of tumor cells, apparently due to a reduction in replication rate. Thus, our findings support the role of protein kinase A as a promising target for novel anti-glioma therapies.

【 授权许可】

Unknown