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Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1
- Source :
- Clinicaltranslational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 21(9)
- Publication Year :
- 2018
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Cancer Research
Epithelial-Mesenchymal Transition
Apoptosis
Metastasis
03 medical and health sciences
0302 clinical medicine
Cell Movement
Stomach Neoplasms
Gene expression
medicine
Tumor Cells, Cultured
Gene silencing
Humans
Neoplasm Invasiveness
Epithelial–mesenchymal transition
Hypoxia
Transcription factor
Cell Proliferation
Gene knockdown
business.industry
General Medicine
Hypoxia (medical)
medicine.disease
Gene Expression Regulation, Neoplastic
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
SNAI1
Cancer research
RNA, Long Noncoding
Snail Family Transcription Factors
medicine.symptom
business
Subjects
Details
- ISSN :
- 16993055
- Volume :
- 21
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Clinicaltranslational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
- Accession number :
- edsair.doi.dedup.....9b5f6f42b711fa4a4e948c8960ae3eeb