Nakashoji Ayako, Hayashida Tetsu, Kawai Yuko, Kikuchi Masayuki, Watanuki Rurina, Yokoe Takamichi, Seki Tomoko, Takahashi Maiko, Miyao Kazuhiro, Yamaguchi Shigeo, Kitagawa Yuko
Department of Surgery, Keio University School of Medicine, Shinanomachi 35 Shinjuku-ku, Tokyo 160-0016, Japan.
J Oncol. 2020 Feb 13;2020:6065736. doi: 10.1155/2020/6065736. eCollection 2020.
First identified as a developmental gene, 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 variant () from human breast cancer cell line-derived mRNA. We confirmed that the novel variant was produced from variationless 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.
最初被鉴定为一种发育基因,已知其也参与肿瘤生物学过程,并且其异常表达与多种癌症的不良预后相关。在本研究中,我们从人乳腺癌细胞系来源的mRNA中分离出一种无同源异型结构域的新型变体(HOXB9v)。我们证实该新型变体由无变异的基因组DNA产生。从临床样本中分离的mRNA的逆转录聚合酶链反应(RT-PCR)以及对公开可用的RNA测序数据的重新分析证明,这种新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被抑制。鉴于HOXB9v缺乏同源异型盒蛋白的关键结构域,其行为可能与先前描述的无变异的HOXB9完全不同。由于先前关于HOXB9的研究均未考虑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。