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Hypoxia Promotes Gastric Cancer Malignancy Partly through the HIF-1 α Dependent Transcriptional Activation of the Long Non-coding RNA GAPLINC

View Article: PubMed Central - PubMed

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 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.

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GAPLINC promoted tumor cell migration and invasion abilities of MKN45 and SGC7901 cells especially under hypoxic conditions. Values represent the mean ± SD. (A,B) Cell migration abilities under nomoxia and hypoxia. (C,D) Cell invasion abilities under nomoxia and hypoxia (*P < 0.05, **P < 0.05).
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Figure 5: GAPLINC promoted tumor cell migration and invasion abilities of MKN45 and SGC7901 cells especially under hypoxic conditions. Values represent the mean ± SD. (A,B) Cell migration abilities under nomoxia and hypoxia. (C,D) Cell invasion abilities under nomoxia and hypoxia (*P < 0.05, **P < 0.05).

Mentions: The cell migration and invasion assays showed similar results (Figures 5A–D and Figure S1). GAPLINC knockdown attenuated cell mobility in 12 and 48 h after seeding. According to the results, cell migration and invasion abilities relied more on GAPLINC under hypoxia than normoxia. These results clearly revealed that GAPLINC could sustain cell survival especially under poor aerobic conditions.


Hypoxia Promotes Gastric Cancer Malignancy Partly through the HIF-1 α Dependent Transcriptional Activation of the Long Non-coding RNA GAPLINC
GAPLINC promoted tumor cell migration and invasion abilities of MKN45 and SGC7901 cells especially under hypoxic conditions. Values represent the mean ± SD. (A,B) Cell migration abilities under nomoxia and hypoxia. (C,D) Cell invasion abilities under nomoxia and hypoxia (*P < 0.05, **P < 0.05).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037220&req=5

Figure 5: GAPLINC promoted tumor cell migration and invasion abilities of MKN45 and SGC7901 cells especially under hypoxic conditions. Values represent the mean ± SD. (A,B) Cell migration abilities under nomoxia and hypoxia. (C,D) Cell invasion abilities under nomoxia and hypoxia (*P < 0.05, **P < 0.05).
Mentions: The cell migration and invasion assays showed similar results (Figures 5A–D and Figure S1). GAPLINC knockdown attenuated cell mobility in 12 and 48 h after seeding. According to the results, cell migration and invasion abilities relied more on GAPLINC under hypoxia than normoxia. These results clearly revealed that GAPLINC could sustain cell survival especially under poor aerobic conditions.

View Article: PubMed Central - PubMed

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-1&alpha; 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-1&alpha; 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.

No MeSH data available.


Related in: MedlinePlus