Hypoxia-induced LncRNA PCGEM1 promotes invasion and metastasis of gastric cancer through regulating SNAI1

• Published in: Clinical & translational oncology Vol. 21; no. 9; pp. 1142 - 1151
• Main Authors: Zhang, J., Jin, H. Y., Wu, Y., Zheng, Z. C., Guo, S., Wang, Y., Yang, D., Meng, X. Y., Xu, X., Zhao, Y.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2019
• Subjects: Apoptosis; Cell Movement; Cell Proliferation; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Hypoxia - physiopathology; Medicine; Medicine & Public Health; Neoplasm Invasiveness; Oncology; Research Article; RNA, Long Noncoding - genetics; Snail Family Transcription Factors - genetics; Snail Family Transcription Factors - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Tumor Cells, Cultured; PCGEM1; SNAI1; Hypoxia; Epithelial–mesenchymal transition; Gastric cancer
• ISSN: 1699-048X; 1699-3055
• DOI: 10.1007/s12094-019-02035-9

Purpose 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). Methods 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. Results 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. Conclusion 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.