title: Hypoxia Promotes Gastric Cancer Malignancy Partly through the HIF-1α Dependent Transcriptional Activation of the Long Non-coding RNA GAPLINC.
abstract: Hypoxia-inducible factor (HIF) activates the transcription of genes involved in cancer progression. Recently, HIF was reported to regulate the transcription of non-coding RNAs. Here, we show that the transcription of a long non-coding RNA (lncRNA), Gastric Adenocarcinoma Associated, Positive CD44 Regulator, Long Intergenic Non-Coding RNA (GAPLINC), is directly activated by HIF-1α in gastric cancer (GC). GAPLINC was overexpressed in GC tissues and promoted tumor migration and invasive behavior. GAPLINC overexpression was associated with poor prognosis in GC patients. Luciferase reporter assays and chromatin immunoprecipitation assays confirmed that HIF-1α binds to the promoter region of GAPLINC and activates its transcription. GAPLINC knockdown inhibited hypoxia-induced tumor proliferationin vivo. Taken together, our results identified a novel role for HIF transcriptional pathways in GC tumorigenesis mediated by the regulation of the lncRNA GAPLINC, and suggest GAPLINC as a novel therapeutic target for reversing chemoradioresistance and prolonging survival.
authors.affiliation: General Surgery Department, Shengjing Hospital, China Medical University Shenyang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Oncology Department, Shengjing Hospital, China Medical University Shenyang, China.
authors.forename: Xihe
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Oncology Department, Shengjing Hospital, China Medical University Shenyang, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Zou
authors.affiliation: General Surgery Department, The Forth Hospital, China Medical University Shenyang, China.
authors.forename: Rubing
authors.initials: R
authors.lastname: Bai
authors.affiliation: General Surgery Department, The Forth Hospital, China Medical University Shenyang, China.
authors.forename: Keyu
authors.initials: K
authors.lastname: Yang
authors.affiliation: General Surgery Department, Shengjing Hospital, China Medical University Shenyang, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Tian
keywords: GAPLINC; HIF-1α; gastric cancer; hypoxia; lncRNA