Journal
EXPERIMENTAL CELL RESEARCH
Volume 368, Issue 2, Pages 194-201Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2018.04.030
Keywords
Chronic hypoxia; UCA1; Hypoxia resistance; MiR-7-5p
Categories
Funding
- National Key Research and Development Program of China [2017YFC1308900]
- Science and Technology Plan Project of Liaoning Province [2015020457, 2016007010]
- National Natural Science Foundation of China [81572374, 81201615]
- Foundation for Selected Overseas Chinese Scholar
- Key Research and Development Program of Shenyang [17-230-9-01]
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A variety of solid tumors are surrounded by a hypoxic microenvironment, which is known to be associated with high metastatic capability and resistance to various clinical therapies, contributing to a poor survival rate for cancer patients. Although the majority of previous studies on tumor-associated hypoxia have focused on acute hypoxia, chronic hypoxia more closely mimics the actual hypoxic microenvironment of a tumor. In this study, two novel hypoxia-resistant gastric cancer (HRGC) cell lines which could grow normally in 2% oxygen were established. The long non-coding RNA UCA1 was upregulated in HRGC cells, which promoted their migration. Bioinformatics analysis and a luciferase reporter assay showed that miR-7-5p could bind to specific sites of UCA1 to regulate the target EGFR through competitive endogenous RNA function. UCA1 directly interacted with miR-7-5p and decreased the binding of miR-7-5p to the EGFR 3'-untranslated region, which suppressed the degradation of EGFR mRNA by miR-7-5p. Therefore, long-term hypoxia induced UCA1 to promote cell migration by enhancing the expression of EGFR. This study thus reveals a new mechanism by which a hypoxic micro environment promotes tumor metastasis, and highlights UCA1 as a potential biomarker for predicting the metastasis of gastric cancer to guide clinical treatment.
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