Protein Arginine Methyltransferase 5 as a Therapeutic Target for KRAS Mutated Colorectal Cancer

摘要

Nearly 45% of colorectal cancer (CRC) patients harbor a mutation in their gene for which, despite many years of research, there are still no targeted therapies available. Protein Arginine Methyltransferase 5 (PRMT5) is a transcription regulator for multiple cellular processes that is currently being tested as a potential target in several cancer types. PRMT5 has been previously shown to be overexpressed in approximately 75% of CRC patient tumor samples, as well as negatively correlated with CRC patient survival. Here, we provide evidence that PRMT5 can act as a surrogate target for mutated in CRC. Our findings show that PRMT5 expression is upregulated, as well as positively correlated with expression, in CRC patient datasets. Moreover, our results reveal that PRMT5 is further overexpressed in mutant CRC cells when compared to wild type (WT) CRC cells at both the transcriptional and translational levels. Additionally, our data demonstrate that this further overexpression of PRMT5 in the mutant CRC cells affects an even greater degree of growth inhibition, apoptosis, and cell cycle arrest, following treatment with PRMT5 inhibitor, when compared to the WT CRC cells. Our research therefore suggests for the first time that PRMT5 and may crosstalk, and thus, PRMT5 can potentially be used as a surrogate target for mutated in CRC.