Posted: Wednesday, August 2, 2023
According to findings presented in Molecular Cell, the minor spliceosome, a key factor in many minor intron-containing genes’ protein expression, may prove to be a valuable target in the treatment of prostate cancer. Downregulation of the minor spliceosome, which seemed to be highest in advanced metastatic prostate cancer, may create disease vulnerability without sacrificing healthy cells.
“The minor spliceosome is enormously important because it particularly processes genes that play a crucial role in cell growth. And it is this cell growth that gets out of control in cancer—but the precise mechanism behind this remained unclear,” noted Rahul N. Kanadia, PhD, of the University of Connecticut, in an institutional press release.
The study demonstrated relationships between minor spliceosome activity, minor intron-containing gene expression, and prostate cancer onset and progression. A key component of the minor spliceosome—known as U6atac snRNA—was also found to be highly expressed in metastasized prostate cancer, reinforcing the minor spliceosome’s impact on disease progression.
Minor spliceosome functions were regulated by androgen receptor signaling during progression to castration-resistant prostate cancer–adenocarcinoma disease and again to castration-resistant prostate cancer–neuroendocrine disease. Because of U6atac snRNA’s critical role in minor spliceosome function, downregulation of U6atac slowed the growth of advanced disease. The efficacy of this treatment bested current therapies such as combination enzalutamide-EZH2 inhibition, according to the investigators.
“We propose that our findings are not limited to [prostate cancer],” concluded the authors. “Current work is now exploring how modulation of [minor spliceosome) can be effectively used to target other cancer.”
Disclosure: For full disclosures of the study authors, visit cell.com.