Long intergenic noncoding RNA 00673 promotes non-small-cell lung cancer metastasis by binding with EZH2 and causing epigenetic silencing of HOXA5.

Chenhui Ma,Dongmei Yuan,Tangfeng Lv,Qingqing Zhu,Yanwen Yao,Yafang Liu,Guannan Wu,Hongbing Liu,Yong Song

doi:10.18632/oncotarget.16158

Abstract

Metastasis of cancer cells is a key impediment to favorable outcomes of cancer treatment. Functional roles of long noncoding RNAs in several biological processes, including metastasis, have recently been discovered. In our previous work, we reported a positive correlation of increased expression of linc00673 in NSCLC tissues with tumor size, lymph node metastasis, TNM stage, and increased proliferation of NSCLC cells, both, in vitro and in vivo. In this study, we demonstrate that ectopic expression of linc00673 promotes migration and invasion of NSCLC cells. Furthermore, our results indicate that linc00673 could silence HOXA5 expression by recruiting epigenetic repressor, EZH2, at its promoter regions. HOXA5 was identified as a tumor suppressor gene, which inhibited NSCLC cell metastasis by regulating cytoskeletal remodeling. To summarize, we for the first time identified the role of lin00673 in promoting invasion and migration of NSCLC cells. Insights from this study may help to identify novel therapeutic targets for NSCLC.

Highlights

Lung cancer is characterized by malignant traits such as tumor heterogeneity, aggressive proliferation, a high propensity for distant metastasis, and associated metabolic disorders
As linc00673 was shown to promote proliferation NSCLC cells, both, in vitro and in vivo, we further investigated its impact on metastasis
Upregulation of linc00673 expression augmented the migratory and invasive abilities of H1703 cells (Figure 1C). These results indicated that linc00673 could promote cancer cell migration and invasion

Summary

Introduction

Lung cancer is characterized by malignant traits such as tumor heterogeneity, aggressive proliferation, a high propensity for distant metastasis, and associated metabolic disorders. It makes sense to study the underlying molecular mechanisms that contribute to aggressive behavior of lung cancer, and may help develop more effective therapeutic approaches. Previous studies have largely focused on the protein-coding genes which could influence every aspect of cancer cell metastasis. Several recent studies have suggested an important role of lncRNAs in mediating tumorigenesis and tumor progression [4,5,6,7]. Wider and further exploration of the expression patterns and molecular mechanisms of lncRNAs may unravel novel targets to prevent proliferation and dissemination of malignant tumor cells

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Conclusion