The long noncoding RNA FOXCUT promotes proliferation and migration by targeting<i>FOXC1</i>in nasopharyngeal carcinoma

Xu, Yuzhong; Chen, Fang‐Fang; Zhao, Qinghao; Guan, Xiao-Long; Li, Ang; Lv, Xin; Song, Shu-Sheng; Zhou, Ying; Li, Xiaojun

doi:10.1177/1010428317706054

Cited by 33 publications

(34 citation statements)

References 28 publications

(38 reference statements)

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“…Recent studies have demonstrated that FOXC1 is highly expressed in various cancers, including NSCLC, and is postulated to be a marker of poor prognosis In the present study, we identified that high FOXC1 expression in NSCLC patients was more frequently associated with adverse clinical parameters and poor OS independent of other clinicopathological prognostic factors, including lymph node status in NSCLC patients. This result was consistent with the conclusion of the study of Cao et al, in which FOXC1 expression was found to be elevated in NSCLC tissues and negatively correlated with patient survival .…”

Section: Discussionsupporting

confidence: 56%

Forkhead box C1 promotes metastasis and invasion of non–small cell lung cancer by binding directly to the lysyl oxidase promoter

et al. 2019

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Increasing evidence indicates that human forkhead box C1 (FOXC1) plays important roles in tumor development and metastasis. However, the underlying molecular mechanism of FOXC1 in non–small cell lung cancer (NSCLC) metastasis remains unclear. Here, we identified FOXC1 as an independent prognostic factor in NSCLC and showed clear biological implications in invasion and metastasis. FOXC1 overexpression enhanced the proliferation, migration and invasion of NSCLC cells, whereas FOXC1 silencing impaired the effects both in vitro and in vivo. Importantly, we found a positive correlation between FOXC1 expression and lysyl oxidase (LOX) expression in NSCLC cells and patient samples. Downregulation of LOX or LOX activity inhibition in NSCLC cells inhibited the FOXC1‐driven effects on cellular migration and invasion. Xenograft models showed that inhibition of LOX activity by β‐aminopropionitrile monofumarate decreased the number of lung metastases. Mechanistically, we demonstrated a novel FOXC1‐LOX mechanism that was involved in the invasion and metastasis of NSCLC. Dual‐luciferase assay and ChIP identified that FOXC1 bound directly in the LOX promoter region and activated its transcription. Collectively, the present study offered new insight into FOXC1 in the mediation of NSCLC metastasis through interaction with the LOX promoter and further revealed that targeted inhibition of LOX protein activity could prevent lung metastasis in murine xenograft models. These data implicated FOXC1 as a potential therapeutic strategy for the treatment of NSCLC metastasis.

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Section: Discussionsupporting

confidence: 56%

Forkhead box C1 promotes metastasis and invasion of non–small cell lung cancer by binding directly to the lysyl oxidase promoter

et al. 2019

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“…The transcription factor FOXC1 is a key regulator of several biological processes and its abnormal expression was found associated to poor survival in various malignant tumors and in the epithelial to mesenchymal transition (EMT) process [24,49,50]. Recent studies showed that the FOXCUT-FOXC1 regulatory network is associated with tumorigenesis and cancer progression in esophageal squamous cell carcinoma (ESCC) [50], oral squamous cell carcinoma (OSCC) [51] and nasopharyngeal carcinoma (NPC) [52].…”

Section: Rna-directed Transcriptional Gene Regulation By Pancrnas In mentioning

confidence: 99%

Dissecting the transcriptional regulatory networks of promoter-associated noncoding RNAs in development and cancer

Chellini

Frezza

Paronetto

2020

J Exp Clin Cancer Res

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In-depth analysis of global RNA sequencing has enabled a comprehensive overview of cellular transcriptomes and revealed the pervasive transcription of divergent RNAs from promoter regions across eukaryotic genomes. These studies disclosed that genomes encode a vast repertoire of RNAs beyond the well-known protein-coding messenger RNAs. Furthermore, they have provided novel insights into the regulation of eukaryotic epigenomes, and transcriptomes, including the identification of novel classes of noncoding transcripts, such as the promoterassociated noncoding RNAs (pancRNAs). PancRNAs are defined as transcripts transcribed within few hundred bases from the transcription start sites (TSSs) of protein-coding or non-coding genes. Unlike the long transacting ncRNAs that regulate expression of target genes located in different chromosomal domains and displaying their function both in the nucleus and in the cytoplasm, the pancRNAs operate as cis-acting elements in the transcriptional regulation of neighboring genes. PancRNAs are very recently emerging as key players in the epigenetic regulation of gene expression programs in development and diseases. Herein, we review the complex epigenetic network driven by pancRNAs in eukaryotic cells, their impact on physiological and pathological states, which render them promising targets for novel therapeutic strategies.

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“…9,10 Recently, increasing evidence has demonstrated that lncRNAs can mediate the progression of tumorigenesis and metastasis in a variety of cancers by dysregulating gene expression at the transcriptional, post-transcriptional or epigenetic level. 12 -14 For example, the expression of lncRNA ANRIL is significantly elevated in NPC tissues, which has been negatively associated with the overall survival of patients, and ANRIL silencing by specific shRNA can effectively inhibit the proliferation and tumorigenesis of NPC cells. 12 -14 For example, the expression of lncRNA ANRIL is significantly elevated in NPC tissues, which has been negatively associated with the overall survival of patients, and ANRIL silencing by specific shRNA can effectively inhibit the proliferation and tumorigenesis of NPC cells.…”

Section: Introductionmentioning

confidence: 99%

“…11 Aberrant expression of lncRNAs has also been involved in the initiation and progression of NPC, as reported by several previous studies. [12][13][14] For example, the expression of lncRNA ANRIL is significantly elevated in NPC tissues, which has been negatively associated with the overall survival of patients, and ANRIL silencing by specific shRNA can effectively inhibit the proliferation and tumorigenesis of NPC cells. 15 Another study by Li, et al 16 also demonstrated the dysregulation of ln-cRNAs, which markedly mediated the progression of NPC, because ln-cRNA-ROR largely promoted proliferation and metastasis through the suppression of the p53 signalling pathway.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA ZFAS1 promotes tumorigenesis and metastasis in nasopharyngeal carcinoma by sponging miR‐892b to up‐regulate LPAR1 expression

Peng

Liu

Zheng

et al. 2019

J Cellular Molecular Medi

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Objective: In this study, we explored the NPC-specific expression of ZFAS1 and the mechanism of ZFAS1-mediated growth, aggressiveness and tumorigenesis in NPC. Methods:The expression profile of lncRNAs was detected in NPC tissues and matching para-carcinoma tissues using microarray analysis. LncRNA-miRNA and miRNA-mRNA interaction networks were constructed using the miRcode v11 and TargetScanHuman v7.2 web server and then validated using dual-luciferase assay.Western blot and RT-qPCR were performed to detect protein and RNA expression.The effects of ZFAS1, miR-892b and LPAR1 dysregulation on the proliferative, migratory and invasive abilities of NPC cells were observed using colony formation, cell counting kit-8 (CCK-8) and transwell assays in vitro. In vivo, a xenograft nude mouse model was established to detect the impact of ZFAS1 dysregulation on the tumorigenicity of NPC cells. Results:The expression of multiple lncRNAs, of which ZFAS1 was up-regulated, was dysregulated in NPC tissues. ZFAS1 directly targeted miR-892b, and miR-892b negatively regulated the expression of downstream LPAR1. The proliferation, migration and invasion of NPC cells could be largely enhanced by the downregulation of miR-892b as well as the up-regulation of ZFAS1 and LPAR1, while the overexpression of miR-892b and the downregulation of ZFAS1 and LPAR1 decreased these abilities.In nude mice, the growth of tumour xenografts formed by HONE1 cells was significantly suppressed when ZFAS1 was silenced. Conclusion:The study demonstrated that lncRNA ZFAS1 may act as a promoter of tumorigenesis and metastasis in nasopharyngeal carcinoma, by up-regulating the expression of LPAR1 in a miR-892b-dependent manner. K E Y W O R D Slong noncoding RNAs, LPAR1, miR-892b, nasopharyngeal carcinoma, ZFAS1

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The long noncoding RNA FOXCUT promotes proliferation and migration by targetingFOXC1in nasopharyngeal carcinoma

Cited by 33 publications

References 28 publications

Forkhead box C1 promotes metastasis and invasion of non–small cell lung cancer by binding directly to the lysyl oxidase promoter

Forkhead box C1 promotes metastasis and invasion of non–small cell lung cancer by binding directly to the lysyl oxidase promoter

Dissecting the transcriptional regulatory networks of promoter-associated noncoding RNAs in development and cancer

Long noncoding RNA ZFAS1 promotes tumorigenesis and metastasis in nasopharyngeal carcinoma by sponging miR‐892b to up‐regulate LPAR1 expression

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