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

• Published in: Oncogene Vol. 35; no. 37; pp. 4927 - 4936
• Main Authors: Huang, B, Song, J H, Cheng, Y, Abraham, J M, Ibrahim, S, Sun, Z, Ke, X, Meltzer, S J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.09.2016; Nature Publishing Group
• Subjects: 13/109; 13/89; 38/1; 38/44; 38/77; 38/89; 38/90; 45/91; 631/67/1504/1829; 631/67/68; 82/1; 82/80; Antisense RNA; Apoptosis; Biomarkers; Carcinogenesis; Carcinogenesis - genetics; Cell Biology; Cell migration; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Development and progression; Disease Progression; Epithelial cells; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Human Genetics; Humans; Internal Medicine; Keratin; Keratin-7 - genetics; Medicine; Medicine & Public Health; Messenger RNA; Non-coding RNA; Oncology; original-article; Post-transcription; Properties; Protein synthesis; Ribonucleic acid; RNA; RNA, Antisense - genetics; RNA, Long Noncoding - genetics; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2016.25

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.