Department of Life Science, Dongguk University-Seoul, Goyang, Republic of Korea.
PanGen Biotech Inc, Suwon, 16675, Republic of Korea.
Sci Rep. 2018 Aug 27;8(1):12922. doi: 10.1038/s41598-018-31306-8.
In our previous study, the Kelch domain-containing 7B (KLHDC7B) was revealed to be hypermethylated at the promoter but upregulated in breast cancer. In this study, we identified a long non-coding RNA, ST8SIA6-AS1 (STAR1), whose expression was significantly associated with KLHDC7B in breast cancer (R = 0.3466, P < 0.01). Involvement of the two genes in tumorigenesis was examined via monitoring their effect on cellular as well as molecular events after each gene dysregulation in cultured mammary cell lines. Apoptosis of MCF-7 decreased by 49.5% and increased by 33.1%, while proliferation noted increase and decrease by up- and downregulation of KLHDC7B, respectively, suggesting its oncogenic property. STAR1, however, suppressed cell migration and increased apoptosis. Network analysis identified many target genes that appeared to have similar regulation, especially in relation to the interferon signaling pathway. Concordantly, expression of genes such as IFITs, STATs, and IL-29 in that pathway was affected by KLHDC7B and STAR1. Taken together, KLHDC7B and STAR1 are both overexpressed in breast cancer and significantly associated with gene modulation activity in the interferon signaling pathway during breast tumorigenesis.
在我们之前的研究中，Kelch 结构域包含 7B（KLHDC7B）在启动子处被高度甲基化，但在乳腺癌中上调。在这项研究中，我们鉴定了一种长非编码 RNA，ST8SIA6-AS1（STAR1），其表达与乳腺癌中的 KLHDC7B 显著相关（R = 0.3466，P < 0.01）。通过监测每个基因在培养的乳腺细胞系中失调后对细胞和分子事件的影响，研究了这两个基因在肿瘤发生中的作用。MCF-7 细胞的凋亡减少了 49.5%，增殖增加了 33.1%，而 KLHDC7B 的上调和下调分别导致细胞增殖增加和减少，表明其具有致癌性。然而，STAR1 抑制细胞迁移并增加细胞凋亡。网络分析确定了许多似乎具有相似调控作用的靶基因，特别是与干扰素信号通路有关。一致地，干扰素信号通路中的 IFITs、STATs 和 IL-29 等基因的表达受到 KLHDC7B 和 STAR1 的影响。总之，KLHDC7B 和 STAR1 在乳腺癌中均过度表达，并且与乳腺癌发生过程中干扰素信号通路中的基因调控活性显著相关。
