Soluble Guanylate Cyclase β1 Subunit Represses Human Glioblastoma Growth

Malignant glioma is the most common and deadly brain tumor. A marked reduction in the levels of sGC (soluble guanylyl cyclase) transcript in the human glioma specimens has been revealed in our previous studies. In the present study, restoring the expression of sGC beta 1 alone repressed the aggressive course of glioma. The antitumor effect of sGC beta 1 was not associated with enzymatic activity of sGC since overexpression of sGC beta 1 alone did not influence the level of cyclic GMP. Additionally, sGC beta 1-induced inhibition of the growth of glioma cells was not influenced by treatment with sGC stimulators or inhibitors. The present study is the first to reveal that sGC beta 1 migrated into the nucleus and interacted with the promoter of the TP53 gene. Transcriptional responses induced by sGC beta 1 caused the G0 cell cycle arrest of glioblastoma cells and inhibition of tumor aggressiveness. sGC beta 1 overexpression impacted signaling in glioblastoma multiforme, including the promotion of nuclear accumulation of p53, a marked reduction in CDK6, and a significant decrease in integrin alpha 6. These anticancer targets of sGC beta 1 may represent clinically important regulatory pathways that contribute to the development of a therapeutic strategy for cancer treatment.

Automated summary

Malignant glioma, the most common and deadly brain tumor, can be suppressed by the expression of sGC beta 1, which is independent of the enzymatic activity and level of cyclic GMP of sGC. sGC beta 1 interacts with the promoter of the TP53 gene, causing G0 cell cycle arrest and inhibiting tumor aggressiveness. Overexpression of sGC beta 1 also affects glioblastoma signaling pathways, including promoting nuclear accumulation of p53, reducing CDK6 expression, and decreasing integrin alpha 6 levels. These findings suggest that sGC beta 1 may be a potential therapeutic target for cancer treatment.