Inhibition of Prostate Cancer with Novel Circular RNA
Novel circular RNA shown to inhibit the viability, migration, invasion, and progression of prostate cancer by its encoded protein
Background
Prostate Cancer (PCa) is the most common cancer diagnosed in men in the USA. There were 191,930 newly diagnosed cases in 2020, accounting for 21% of all cases.
PCa is often multifocal, having topographically and morphologically distinct tumor foci. Different tumor foci within the same patients have been reported to be genetically distinct. The multifocal and heterogeneous nature of PCa are important contributors to the difficulties associated with diagnosis and treatment.
Technology Overview
Circular RNAs are a family of endogenous RNAs which have become a focus of biological research in recent years. As they are involved in the progression of cell proliferation, apoptosis, metastasis, and therapy resistance in PCa, circular RNAs have been promoted as cancer diagnostic markers and therapeutic targets. Most studies demonstrate that circular RNAs exert their regulatory functions through miRNA sponging or protein binding.
Researchers have discovered a novel circular RNA, circCCDC715-19, that is a bona fide tumor suppressor gene, encoding a protein which is the mechanism of action for its tumor suppressive activity ().
CircCCDC715-19 is downregulated in PCa, and its expression is associated with better prognosis (, , ).
CircCCDC715-19 has also been shown to inhibit the viability, migration, and invasion of PCa. Colony formation assays measuring cell viability in DU145 and PC3 cell lines demonstrated that circCCDC715-19 has an inhibitory effect on cell viability (). Transwell assays showed that circCCDC715-19 suppresses the migration and invasion of both DU145 and PC3 cells ().
CircCCDC715-19 inhibits the viability, migration, and invasion of PCa and plays an important role in tumorigenesis in vivo ().
ICircCCDC715-19 suppresses the progression of PCa by its encoded protein (). A frame shift mutant of circCCDC715-19 did not affect the viability of PCa, while the wild-type circCCDC715-19 decreased the viability significantly. Similarity, transwell assay demonstrated circCCDC715-19 with frame shift mutation lost its inhibitory function on migration and invasion of PCa. FLRT3 is a downstream target of circCCDC715-19. Knocking down FLRT3 rescues the effect of circCCDC715-19 on PCa.