LncRNA FTX activates FOXA2 expression to inhibit non-small-cell lung cancer proliferation and metastasis.

Shidai Jin,Deqin Wu,Jing He,Jun Li,Wen Gao,Yue Zhou

doi:10.1111/jcmm.15163

Shidai Jin, Deqin Wu + Show 4 more

Open Access

https://doi.org/10.1111/jcmm.15163

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Abstract

Lung cancer leads to the highest mortality among all cancer types in the world, and non–small‐cell lung cancer (NSCLC) occupies over 80% of the lung cancer cases. Numerous studies have demonstrated that long non‐coding RNA (lncRNA) is involved in various human diseases including cancer. LncRNA FTX was firstly identified in Xist gene locus and was dysregulated in many human cancers. However, the function of FTX in NSCLC is still unclear. Here, we report that long non‐coding RNA FTX expression level is down‐regulated in NSCLC clinical tissue samples and cell lines. Ectopic expression of FTX inhibits proliferation and metastasis of lung cancer cells in vitro and in vivo. Furthermore, we find that FTX overexpression activates the expression of transcription factor FOXA2, an important regulator in lung cancer progression, and we reveal a novel FTX/miR‐200a‐3p/FOXA2 competing endogenous RNA regulatory axis in lung cancer cells. Our results provide new insights and directions for exploring the function of FTX in lung cancer progression.

Highlights

Lung cancer is one of the most common cancers in the world and leads to the highest mortality in the past decades.[1]
We found that FTX expression was decreased in non–small-cell lung cancer (NSCLC) clinical tissue samples and cell lines
We verified that FTX expression was decreased in NSCLC tissue samples and cell lines

Summary

| INTRODUCTION

Lung cancer is one of the most common cancers in the world and leads to the highest mortality in the past decades.[1]. Whether lncRNA FTX participates in lung cancer progression and the possibility for FTX to act as a prognostic marker remain unclear. We found that FTX expression was decreased in NSCLC clinical tissue samples and cell lines. FTX overexpression inhibited lung cancer cell proliferation and metastasis via interacting with miR-200a-3p to promote FOXA2 expression, suggesting that FTX may act as a tumour suppressor in lung cancer progression. Wild-type and mutant FTX gene or FOXA2 3’-UTR sequences were individually synthesized by GenePharm and cloned into pGL3-basic luciferase reporter vector (Promega) for the following luciferase assay. Cell growth of lung cancer cells was examined by the Cell Counting Kit-8 (CCK-8, Dojindo) and EdU Cell Proliferation Kit (Ribobio) following the manufacturers’ instructions. Cell cycle was assessed using the Cell Cycle Detection Kit (KeyGEN BioTECH)

| MATERIALS AND METHODS

Findings

| DISCUSSION