A Newly Identified lncBCAS1-4_1 Associated With Vitamin D Signaling and EMT in Ovarian Cancer Cells

Abstract

Long noncoding RNAs (lncRNAs) were identified rapidly due to their important role in many biological processes and human diseases including cancer. 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3] and its analogues are widely applied as preventative and therapeutic anticancer agents. However, the expression profile of lncRNAs regulated by 1α,25(OH)2D3 in ovarian cancer remains to be clarified. In the present study, we found 606 lncRNAs and 102 mRNAs that showed differential expression (DE) based on microarray data. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DE genes were mainly enriched in TGF-β, MAPK, Ras, PI3K-Akt, and Hippo signaling pathways, as well as the vitamin D-related pathway. We further assessed the potential lncRNAs that linked vitamin D signaling with EMT, and lncBCAS1-4_1 was identified in the first time. Moreover, we found that the most upregulated lncBCAS1-4_1 showed 75% same transcripts with CYP24A1 (metabolic enzyme of 1α,25(OH)2D3). Finally, the lncBCAS1-4_1 gain-of-function cell model was established, which demonstrated that the knockdown of lncBCAS1-4_1 inhibited the proliferation and migration of ovarian cancer cells. Furthermore, lncBCAS1-4_1 could resist the antitumor effect of 1α,25(OH)2D3, which was associated with upregulated ZEB1. These data provide new evidences that lncRNAs served as a target for the antitumor effect of 1α,25(OH)2D3.