A Kelch domain-containing KLHDC7B and a long non-coding RNA ST8SIA6-AS1 act oppositely on breast cancer cell proliferation via the interferon signaling pathway

Abstract

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-2 = 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.