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

HO HYUNG WOO, SETSUKO K. CHAMBERS

Research output: Contribution to journalArticlepeer-review

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 the 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 the 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 in up-regulation 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, down-regulates 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 the HMGXB3 gene can influence the expression of adjacent c-fms mRNA, or vice versa.

Original languageEnglish (US)
Pages (from-to)1068-1081
Number of pages14
JournalRNA
Volume27
Issue number9
DOIs
StatePublished - Sep 2021
Externally publishedYes

Keywords

  • Convergent transcription termination; sense-antisense RNA pairing; mRNA 3' end polymorphism; c-fms mRNA 3' end; HMGXB3 mRNA 3' end

ASJC Scopus subject areas

  • Molecular Biology

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