title: 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.
authors.affiliation: Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.|Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: B
authors.initials: B
authors.lastname: Huang
authors.affiliation: Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Song
authors.affiliation: Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Abraham
authors.affiliation: Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ibrahim
authors.affiliation: Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Ke
authors.affiliation: Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Meltzer
mesh_terms: D063646:Carcinogenesis / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053552:Keratin-7 / Q000235:genetics*; D016372:RNA, Antisense / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: C507497:KRT7 protein, human; D053552:Keratin-7; D016372:RNA, Antisense; D062085:RNA, Long Noncoding