LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer

Abstract

AbstractMetastasis constitutes one of the major causes of tumor-related death in gastric cancer (GC), and understanding key events in the initiation of this phenotypic switch may provide therapeutic opportunities. Long noncoding RNAs (lncRNAs) are emerging as molecules that play vital roles in tumorigenesis and metastasis. In this study, we aimed to identify metastasis-related lncRNAs in the context of GC. The lncRNAs overexpressed in tumor tissues and positively associated with overall survival were screened out using the TCGA database. qPCR assays in clinical samples showed that LINC00858 was significantly upregulated in GC tissues compared with normal counterparts. Functional analysis suggested that LINC00858 depletion attenuated the migration, and invasion of cancer cells in vitro and suppressed the metastasis of xenografted tumors in vivo. Mechanistically, LINC00858 could interact with the metastasis-associated RAN and stabilize its protein expression by decreasing posttranslational ubiquitination. The transcription factor YY1 could bind to the promoter of LINC00858 to upregulate its expression in GC cells. Moreover, overexpression of YY1 and RAN was positively associated with upregulation of LINC00858 in GC tissues. Our results suggest that LINC00858 might play a role in GC metastasis, and be a diagnostic biomarker and potential therapeutic target.