Identification of a Modified HOXB9 mRNA in Breast Cancer
Identification of a Modified HOXB9 mRNA in Breast Cancer
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DOI：
10.1155/2020/6065736
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发表时间：
2020-02
影响因子：
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通讯作者：
Ayako Nakashoji;T. Hayashida;Y. Kawai;Masayuki Kikuchi;R. Watanuki;Takamichi Yokoe;T. Seki;Maiko Takahashi;Kazuhiro Miyao;Shigeo Yamaguchi;Y. Kitagawa
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文献类型：
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作者：
Ayako Nakashoji;T. Hayashida;Y. Kawai;Masayuki Kikuchi;R. Watanuki;Takamichi Yokoe;T. Seki;Maiko Takahashi;Kazuhiro Miyao;Shigeo Yamaguchi;Y. Kitagawa
HOXB9最初被鉴定为一种发育基因，也已知参与肿瘤生物学过程，其异常表达与多种癌症的不良预后相关。在这项研究中，我们从人乳腺癌细胞系来源的mRNA中分离出一种无同源结构域的新型HOXB9变体（HOXB9v）。我们证实这种新型变体是由无变异的HOXB9基因组DNA产生的。对从临床样本中分离的mRNA进行逆转录聚合酶链反应（RT - PCR）以及对公开可用的RNA - seq数据的重新分析证明，这种新的转录本在人乳腺癌中频繁表达。外源性HOXB9v表达显著增强了乳腺癌细胞的增殖，基因本体分析表明这些细胞中的凋亡信号受到抑制。考虑到HOXB9v缺乏同源框蛋白的关键结构域，其行为可能与先前描述的无变异的HOXB9完全不同。由于之前关于HOXB9的研究都没有考虑到HOXB9v的存在，因此有必要进一步分别分析这两种转录本，以重新评估HOXB9在癌症中的真正作用。
First identified as a developmental gene, HOXB9 is also known to be involved in tumor biological processes, and its aberrant expression correlates with poor prognosis of various cancers. In this study, we isolated a homeodomain-less, novel HOXB9 variant (HOXB9v) from human breast cancer cell line-derived mRNA. We confirmed that the novel variant was produced from variationless HOXB9 genomic DNA. RT-PCR of mRNA isolated from clinical samples and reanalysis of publicly available RNA-seq data proved that the new transcript is frequently expressed in human breast cancer. Exogenous HOXB9v expression significantly enhanced the proliferation of breast cancer cells, and gene ontology analysis indicated that apoptotic signaling was suppressed in these cells. Considering that HOXB9v lacks key domains of homeobox proteins, its behavior could be completely different from that of the previously described variationless HOXB9. Because none of the previous studies on HOXB9 have considered the presence of HOXB9v, further research analyzing the two transcripts individually is warranted to re-evaluate the true role of HOXB9 in cancer.