Hypoxia promotes gastric cancer malignancy partly through the HIF-1α dependent transcriptional activation of the long non-coding RNA GAPLINC
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 Re...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-09-01
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| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00420/full |
| _version_ | 1818067747135815680 |
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| author | Lei Liu Xihe Zhao Huawei Zou Rubing Bai Keyu Yang Zhong Tian |
| author_facet | Lei Liu Xihe Zhao Huawei Zou Rubing Bai Keyu Yang Zhong Tian |
| author_sort | Lei Liu |
| collection | DOAJ |
| description | 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 in 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. |
| first_indexed | 2024-12-10T15:28:35Z |
| format | Article |
| id | doaj.art-ed61e4dc7e234e549089770427b3d914 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-10T15:28:35Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-ed61e4dc7e234e549089770427b3d9142022-12-22T01:43:29ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-09-01710.3389/fphys.2016.00420214688Hypoxia promotes gastric cancer malignancy partly through the HIF-1α dependent transcriptional activation of the long non-coding RNA GAPLINCLei Liu0Xihe Zhao1Huawei Zou2Rubing Bai3Keyu Yang4Zhong Tian5China medical University Shengjing HospitalChina Medical University Shengjing HospitalChina Medical University Shengjing HospitalChina Medical University The Forth HospitalChina Medical University The Forth HospitalChina medical University Shengjing HospitalHypoxia-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 in 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.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00420/fullhypoxialncRNAgastric cancerHIF-1αGAPLINC |
| spellingShingle | Lei Liu Xihe Zhao Huawei Zou Rubing Bai Keyu Yang Zhong Tian Hypoxia promotes gastric cancer malignancy partly through the HIF-1α dependent transcriptional activation of the long non-coding RNA GAPLINC Frontiers in Physiology hypoxia lncRNA gastric cancer HIF-1α GAPLINC |
| title | Hypoxia promotes gastric cancer malignancy partly through the HIF-1α dependent transcriptional activation of the long non-coding RNA GAPLINC |
| title_full | Hypoxia promotes gastric cancer malignancy partly through the HIF-1α dependent transcriptional activation of the long non-coding RNA GAPLINC |
| title_fullStr | Hypoxia promotes gastric cancer malignancy partly through the HIF-1α dependent transcriptional activation of the long non-coding RNA GAPLINC |
| title_full_unstemmed | Hypoxia promotes gastric cancer malignancy partly through the HIF-1α dependent transcriptional activation of the long non-coding RNA GAPLINC |
| title_short | Hypoxia promotes gastric cancer malignancy partly through the HIF-1α dependent transcriptional activation of the long non-coding RNA GAPLINC |
| title_sort | hypoxia promotes gastric cancer malignancy partly through the hif 1α dependent transcriptional activation of the long non coding rna gaplinc |
| topic | hypoxia lncRNA gastric cancer HIF-1α GAPLINC |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00420/full |
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