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. 2018 Jul 15;368(2):194-201.
doi: 10.1016/j.yexcr.2018.04.030. Epub 2018 May 1.

Long non-coding RNA UCA1 upregulation promotes the migration of hypoxia-resistant gastric cancer cells through the miR-7-5p/EGFR axis

Zichang Yang  1 , Xiaonan Shi  1 , Ce Li  1 , Xiaoxun Wang  1 , Kezuo Hou  1 , Zhi Li  1 , Xiaojie Zhang  1 , Yibo Fan  1 , Xiujuan Qu  1 , Xiaofang Che  2 , Yunpeng Liu  3
Affiliations

Long non-coding RNA UCA1 upregulation promotes the migration of hypoxia-resistant gastric cancer cells through the miR-7-5p/EGFR axis

Zichang Yang et al. Exp Cell Res. .

Abstract

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 microenvironment promotes tumor metastasis, and highlights UCA1 as a potential biomarker for predicting the metastasis of gastric cancer to guide clinical treatment.

Keywords: Chronic hypoxia; Hypoxia resistance; MiR-7-5p; UCA1.

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