Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression

Abstract

Alterations in long non-coding RNAs (lncRNAs) are associated with human carcinogenesis. One group of lncRNAs, which are antisense in orientation to coding mRNAs (ASs), have been recently described in cancers but are poorly understood. We sought to identify ASs involved in human gastric cancer (GC) and to elucidate their mechanisms of action in carcinogenesis. We performed massively parallel RNA sequencing in GCs and matched normal tissues, as well as in GC-derived and normal gastric epithelial cell lines. One AS, designated Homo sapiens keratin 7 (KRT7-AS), was selected due to its marked upregulation and concordant expression with its cognate sense counterpart, KRT7, in GC tissues and cell lines. KRT7-AS formed an RNA-RNA hybrid with KRT7 and controlled KRT7 expression at both the mRNA and the post-transcriptional levels. Moreover, forced overexpression of the KRT7-overlapping region (OL) of KRT7-AS (but not its non-KRT7-OL portions) increased keratin 7 protein levels in cells. Finally, forced overexpression of full-length KRT7-AS or OL KRT7-AS (but not its non-KRT7-OL regions) promoted GC cell proliferation and migration. We conclude that lncRNA KRT7-AS promotes GC, at least in part, by increasing KRT7 expression.