Liu Lei, Zhao Xihe, Zou Huawei, Bai Rubing, Yang Keyu, Tian Zhong
General Surgery Department, Shengjing Hospital, China Medical University Shenyang, China.
Oncology Department, Shengjing Hospital, China Medical University Shenyang, China.
Front Physiol. 2016 Sep 27;7:420. doi: 10.3389/fphys.2016.00420. eCollection 2016.
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 proliferation . 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.
缺氧诱导因子（HIF）可激活参与癌症进展的基因转录。最近，有报道称HIF可调控非编码RNA的转录。在此，我们发现一种长链非编码RNA（lncRNA），即胃癌相关、阳性CD44调节因子、长链基因间非编码RNA（GAPLINC）的转录在胃癌（GC）中被HIF-1α直接激活。GAPLINC在GC组织中过表达，并促进肿瘤迁移和侵袭行为。GAPLINC过表达与GC患者的不良预后相关。荧光素酶报告基因检测和染色质免疫沉淀检测证实，HIF-1α与GAPLINC的启动子区域结合并激活其转录。GAPLINC敲低可抑制缺氧诱导的肿瘤增殖。综上所述，我们的研究结果确定了HIF转录通路在由lncRNA GAPLINC调控介导的GC肿瘤发生中的新作用，并表明GAPLINC是逆转放化疗耐药性和延长生存期的新治疗靶点。
