LncRNA FTX activates FOXA2 expression to inhibit non–small‐cell lung cancer proliferation and metastasis

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. K E Y W O R D S FOXA2, FTX, miR-200a-3p, non-small-cell lung cancer How to cite this article: Jin S, He J, Zhou Y, Wu D, Li J, Gao W. LncRNA FTX activates FOXA2 expression to inhibit nonsmall-cell lung cancer proliferation and metastasis. J Cell Mol Med. 2020;24:4839-4849. https://doi.

Long noncoding RNA TSLNC8 enhances pancreatic cancer aggressiveness by regulating CTNNB1 expression via association with HuR

“…Consistent with our nding, some lncRNAs have been found to exert opposite effects in different types of human cancers. For example, lncRNA FTX upregulates FOXA2 expression to suppress non-smallcell lung cancer progression (22). Nevertheless, lncRNA FTX inhibits phosphorylation of vimentin for promoting colorectal cancer metastasis (23).…”

Lnc-HSD17B11-1:1 Functions as a Competing Endogenous RNA to Promote Colorectal Cancer Progression by Sponging miR-338-3p to Upregulate MACC1

“…Some lncRNAs were reported to function as oncogenes or tumor suppressors in different types of cancers including CRC (Jin et al, 2020;Shang et al, 2020;Shen et al, 2020;Wang et al, 2020;Wei et al, 2020;Zheng et al, 2020). only few lncRNAs in CRC have been functionally characterized and the biological function of most of the lncRNAs remains largely unknown.…”

LncRNAs in Non-Small-Cell Lung Cancer

“…LncRNA Fork-head box F1 (FOXF1) antisense RNA 1 (FOXF1-AS1) also inhibited EMT by directing EZH2 repression of FOXF1 expression to inhibit migration and invasion of NSCLC cells [103]. LncRNA FTX transcript, XIST regulator (FTX) acted as a ceRNA for miR-200a-3p to increase Fork-head box protein A2 (FOXA2) to inhibit NSCLC cell EMT and metastasis [104]. Interestingly, the miR-200 family is generally associated with tumor suppressors and oncogenic lncRNAs such as PVT1 silence miR-200a and miR-200b to enhance NSCLC tumorigenesis [80].…”

“…Interestingly, the miR-200 family is generally associated with tumor suppressors and oncogenic lncRNAs such as PVT1 silence miR-200a and miR-200b to enhance NSCLC tumorigenesis [80]. As FTX also inhibits miR-200 family member miR-200a-3p to suppress NSCLC progression, it suggests that miRNA regulation by lncRNAs is complex in NSCLC [104]. GAS5 antisense RNA 1 (GAS5-AS1) also inhibited NSCLC cell EMT to inhibit migration and invasion of NSCLC cells [106].…”