Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1
Hypoxia is an indispensable factor in the progression of metastasis. Hypoxia inducible factor-1α (HIF-1α), the core element in generating the hypoxia response, induces invasion and metastasis by promoting epithelial–mesenchymal transition (EMT). This study explored the underlying mechanism of hypoxia associated with the invasion and metastasis of gastric cancer (GC).
Six methods were employed to assess the function of the long noncoding RNA (lncRNA) prostate cancer gene expression marker 1 (PCGEM1) including gene silencing, RT-PCR, the separation of nuclear and cytoplasmic fractions, scrape motility assay, transwell migration assay, and Western-blot.
LncRNA PCGEM1 was overexpressed in GC cells and tissues, and was induced by hypoxia in GC cells. Additional experiments confirmed that the knockdown of PCGEM1 significantly repressed the invasion and metastasis of GC cells. SNAI1, a key transcription factor of EMT, was regulated by PCGEM1. Overexpression of SNAI1 rescued the inhibition of PCGEM1-knockdown during the invasion and metastasis of GC cells. In addition, PCGEM1 and SNAI1 jointly affected the biomarkers of EMT.
Our findings indicated that PCGEM1 is a hypoxia-responsive lncRNA, and contributes to the invasion and metastasis of GC. The potential mechanism is attributed to the regulation of EMT by PCGEM1 and its influence on the expression of SNAI1.
KeywordsGastric cancer Hypoxia PCGEM1 SNAI1 Epithelial–mesenchymal transition
ZJ performed the majority of experiments and analyzed the data and drafted the manuscript; ZZC, ZY designed the research; WY, YD, MXY conducted the molecular biology assays and assisted in writing the manuscript; GS, WY collected and analyzed the data; ZY provided critical revision of the manuscript for important intellectual content. JHY provided critical revision of the manuscript for important intellectual content.
Liaoning S&T Project (20180550971). Liaoning provincial special Fund for central guiding local science and technology development plan (2018416017)
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest related to this study.
Informed consent was obtained from all individual participants included in the study.
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