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Regulation of closely juxtaposed proto-oncogene c-fms and HMGXB3 gene expression by mRNA 3′ end polymorphism in breast cancer cells
RNA ( IF 4.2 ) Pub Date : 2021-09-01 , DOI: 10.1261/rna.078749.121
Ho-Hyung Woo 1 , Setsuko K Chambers 1, 2
Affiliation  

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.

中文翻译:

乳腺癌细胞中mRNA 3'末端多态性对紧密并列的原癌基因c-fms和HMGXB3基因表达的调控

聚合转录产生的正义-反义mRNA对是一种基因调控方式。c-fms基因与HMGXB3基因在相反方向紧密并列,在 5 号染色体上。c-fmsHMGXB3基因之间的基因间区域 (IR) 为 162 bp。我们发现一小部分 (~4.18%) HMGXB3 mRNA 被进一步转录到下游,包括产生针对c-fms mRNA 的反义 mRNA的c-fms基因的末端。类似地,一小部分(~1.1%)的c-fms mRNA 被进一步转录到下游,包括HMGXB3基因的末端,产生针对HMGXB3的反义 mRNAmRNA。在 IR 中插入强 poly(A) 信号序列导致c-fmsHMGXB3反义 mRNA 减少,从而导致c-fmsHMGXB3 mRNA 表达上调。miR-324-5p 靶向HMGXB3 mRNA 3' UTR,因此调节c-fms mRNA 表达。HuR 稳定c-fms mRNA,因此下调HMGXB3 mRNA 表达。UALCAN 分析表明,c-fms和 HMGXB3 蛋白之间的表达模式在体内在乳腺癌组织中是相反的。总之,我们的结果表明HMGXB3编码的 mRNA基因可以影响相邻c-fms mRNA的表达,反之亦然。
更新日期:2021-08-16
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