The PAX‐5 transcript is submitted to 3'UTR editing which regulates its oncogenic expression in cancer cells

Abstract

The Pax‐5 oncogene is a major factor in various cancer lesions such as hematopoietic cancers. Recently, we have also shown that Pax‐5 regulates breast cancer phenotypic transitioning processes (EMT‐MET) leading to the regulation of cancer cell malignancy. To date, the aberrant expression of Pax‐5 in cancer cells is still unknown. Our team has thus turned its attention to the post‐transcriptional regulation of Pax‐5 expression by important regulatory elements such as miRNAs and alternative polyadenylation (APA). Upon our analysis of the Pax‐5 transcript in Pax‐5 bearing cells (breast epithelia and B lymphocytes), we found that not only is the 3'UTR submitted to APA; but also, alternative splicing of the Pax‐5 mRNA 3'UTR. Interestingly, upon rapid amplification of cDNA ends (3'RACE) from polysomal fractions, we found that Pax‐5 3'UTR shortening correlates with increased translation frequency. These observations were also validated using reporter gene assays where various truncated 3'UTRs cloned downstream of a luciferase gene resulted in differentially translational expression. More importantly, we also found that Pax‐5 transcripts characterized with shorter 3'UTRs were also associated with advanced staging of hematopoietic cancer lesions. Our findings identify novel molecular mechanisms, which account for Pax‐5 aberrant expression and function in cancer cells. These findings will further elucidate Pax‐5‐mediated cancer processes and may provide new avenues for therapeutic intervention.Support or Funding InformationThis work was supported by grants from the New Brunswick (NB) Innovation Foundation, the Canadian Breast Cancer Foundation, the Canadian Breast Cancer Society/QEII Foundation, the NB Health Research Foundation and by the Beatrice Hunter Cancer Research InstituteThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.