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

Oncogene volume 35, pages 4927–4936 (2016)Cite this article

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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.

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Acknowledgements

SJM, the Harry and Betty Myerberg/Thomas R Hendrix Professor of Gastroenterology, is also an American Cancer Society Clinical Research Professor and was supported by NIH grants CA190040, CA85069, DK087454, CA133012, CA173390, and Sidney Kimmel Comprehensive Cancer Center Core facilities. BH was supported by an Exchange Scholarship from the China Scholarship Council (CSC). BH is a recipient of a Joint Johns Hopkins University-Tongji University of China student scholarship. BH was supported by an Exchange Scholarship from the China Scholarship Council (CSC).

Author contributions

This study was conceived by BH, JHS, YC and SJM. All authors contributed to study design as well as to acquisition of samples or data. The data were analyzed and interpreted by BH, JHS and SJM. This article was drafted by BH and SJM, and was reviewed and approved by all authors in the current format. All who made significant contributions are listed as authors.

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  1. B Huang and J H Song: Share co-first authorship.

Authors and Affiliations

  1. Department of Gastroenterology, Tongji Hospital, Tongji University School of Medicine, Shanghai, China

    B Huang

  2. Division of Gastroenterology, Departments of Medicine and Oncology and Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    B Huang, J H Song, Y Cheng, J M Abraham, S Ibrahim, Z Sun, X Ke & S J Meltzer

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Huang, B., Song, J., Cheng, Y. et al. Long non-coding antisense RNA KRT7-AS is activated in gastric cancers and supports cancer cell progression by increasing KRT7 expression. Oncogene 35, 4927–4936 (2016). https://doi.org/10.1038/onc.2016.25

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