Regulation of closely juxtaposed protooncogene c-fms and HMGXB3 gene expression by mRNA 3’end polymorphism in breast cancer cells

Abstract

Sense-antisense mRNA pairs generated by convergent transcription is a way of gene regulation. c-fms gene is closely juxtaposed to the HMGXB3 gene in the opposite orientation, in chromosome 5. The intergenic region (IR) between c-fms and HMGXB3 genes is 162 bp. We found that a small portion (~4.18%) of HMGXB3 mRNA is transcribed further downstream including the end of c-fms gene generating antisense mRNA against c-fms mRNA. Similarly, a small portion (~1.1%) of c-fms mRNA is transcribed further downstream including the end of HMGXB3 gene generating antisense mRNA against the HMGXB3 mRNA. Insertion of the strong poly-A signal sequence in the IR results in decreased c-fms and HMGXB3 antisense mRNAs, resulting upregulation of both c-fms and HMGXB3 mRNA expression. miR-324-5p targets HMGXB3 mRNA 3’UTR, and as a result, regulates c-fms mRNA expression. HuR stabilizes c-fms mRNA, and as a result, downregulates HMGXB3 mRNA expression. UALCAN analysis indicates that the expression pattern between c-fms and HMGXB3 proteins are opposite in vivo in breast cancer tissues. Together, our results indicate that the mRNA encoded by HMGXB3 gene can influence the expression of adjacent c-fms mRNA, or vice versa.