The expression and functional role of a FOXC1 related mRNA-lncRNA pair in oral squamous cell carcinoma

Kong, Xiangpan; Yao, Jie; Luo, Wei; Feng, Fu-Kui; Ma, Junxun; Ren, Yipeng; Wang, Deli; Bu, Rongfa

doi:10.1007/s11010-014-2093-4

Cited by 58 publications

(61 citation statements)

References 22 publications

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“…FOXCUT is a novel lncRNA (NR_125804.1) located on chromosome 6p25 and upstream of the FOXC1 promoter. Previous studies showed that the FOXCUT-FOXC1 regulatory network is associated with tumorigenesis and cancer progression in oral squamous cell carcinoma and breast cancer; 12,13 however, the function of the FOXCUT-FOXC1 pair in NPC has not been described. In this study, we investigated the expression levels and clinicopathological characteristics of the FOXCUT-FOXC1 pair in NPC and explored the role of FOXCUT in cell proliferation and migration associated with NPC to evaluate its efficacy as a potential therapeutic target.…”

Section: Introductionmentioning

confidence: 99%

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

Chen

Zhao

et al. 2017

Tumour Biol.

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Long noncoding RNAs play an important role in various biological processes, including tumorigenesis. FOXC1 (Forkhead box C1) is a member of the Forkhead box family of transcription factors and plays a crucial role in nasopharyngeal carcinoma. In this study, a novel long noncoding RNA (FOXCUT) located upstream of FOXC1 was investigated in 42 nasopharyngeal carcinoma patients. Our analysis revealed that the expression levels of FOXCUT and FOXC1 in nasopharyngeal carcinoma tissues were significantly higher than those observed in chronic nasopharyngitis tissues and that FOXCUT expression was positively correlated with FOXC1 expression. Additionally, knockdown of FOXCUT significantly inhibited proliferation and migration of nasopharyngeal carcinoma cell lines and resulted in downregulated expression of the matrix metalloproteinase 7 and matrix metalloproteinase 9, as well as vascular endothelial growth factor A and β-catenin. Our findings suggested that FOXCUT expression contributed to the development and progression of nasopharyngeal carcinoma by targeting FOXC1 and that FOXCUT might be useful as a potential nasopharyngeal carcinoma biomarker and therapeutic target.

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Section: Introductionmentioning

confidence: 99%

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

Chen

Zhao

et al. 2017

Tumour Biol.

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“…They also reported metastasis‐associated lung adenocarcinoma transcript 1 (MALAT‐1) was overexpressed and MEG3 was attenuated in TSCCs (Fang et al., ). The long non‐coding RNA FOXCUT (FOXC1 promoter upstream transcript) and its neighboring gene FOXC1 were upregulated in OSCC, and knockdown of either of them inhibited cell proliferation, colony formation, migration, and invasion (Kong et al., ). LncRNA SOX2 overlapping transcript (SOX2OT) has two splice variants (SOX2OT‐S1 and SOX2OT‐S2) which were co‐upregulated with master regulators of pluripotency, SOX2 and OCT4, in ESCC tissue samples.…”

Section: Introductionmentioning

confidence: 99%

Role of non‐coding RNAs in head and neck squamous cell carcinoma: A narrative review

et al. 2017

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Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with high recurrence, metastasis, and poor treatment outcome. Recent studies have reported that non-coding RNA (ncRNA) might play critical role in regulating different types of cancer. MicroRNAs (miRs) are short ncRNAs (20-25 nucleotides) responsible for post-transcriptional regulation of gene expression and may have a role in oncogenesis by acting as oncomiRs or tumor suppressor miRs. Long non-coding RNAs (lncRNAs) are heterogenous group of ncRNAs more than 200 nucleotides long, can act in cis and/or in trans, and have been also implicated in carcinogenesis. These molecules have been suggested to be promising candidates as diagnostic and prognostic biomarkers and for development of novel therapeutic approaches. In this review, we have summarized recent findings on role of these ncRNAs in HPV-negative (HPV-ve) and HPV-positive (HPV+ve) HNSCC. The available literature supports differential expression of both microRNAs and long non-coding RNAs, which include oncogenic ncRNAs (miR-21, miR-31, miR-155, miR-211, HOTAIR, and MALAT1) and tumor suppressor ncRNAs (let7d, miR-17, miR-375, miR-139, and MEG3) in HPV+ve HNSCC tumors as compared to HPV-ve tumors and they have distinct role in the pathophysiology of these two types of HNSCCs.

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“…However, our result is contradictory to studies of FOXC1 in nasopharyngeal cancers, as studies show that reduced FOXC1 in nasopharyngeal cancers cells are associated with a decrease in MMP9. 24,25 These differences are likely due to the use of different cell lines and tissues of origin used in these studies, again suggesting a tissue-specific role of FOXC1 in disease pathogenesis. This is the first study illustrating a link between FOXC1 and the prostaglandin signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost

Doucette

Footz

Walter

2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. This study examines the effect of FOXC1 on the prostaglandin pathway in order to explore FOXC1's role in the prostaglandin-resistant glaucoma phenotype commonly seen in Axenfeld-Rieger syndrome.METHODS. Binding and transcriptional activity of FOXC1 to the gene coding for the EP3 prostaglandin receptor (PTGER3) were evaluated through ChIP-qPCR and luciferase-based assays. Immortalized trabecular meshwork cells (TM1) and HeLa cells had FOXC1 mRNA reduced via siRNA interference. qPCR and Western blot experiments were conducted to examine the changes in prostaglandin receptor expression brought about by lowered FOXC1. TM1 cells were then treated with 10 lM latanoprost acid and/or an siRNA for FOXC1. The expression of fibronectin and matrix metalloproteinase 9 were evaluated via qPCR in each treatment condition.RESULTS. ChIP-qPCR and luciferase experiments confirmed that FOXC1 binds to and activates transcription of the EP3 gene prostaglandin receptor. qPCR and Western experiments in HeLa and TM1 cells showed that FOXC1 siRNA knockdown results in significantly lowered EP3 levels (protein and RNA). In addition, RNA levels of the other prostaglandin receptor genes EP1 (PTGER1), EP2 (PTGER2), EP4 (PTGER4), and FP (PTGFR) were altered when FOXC1 was knocked down in TM1 and HeLa cells. Analysis of fibronectin expression in TM1 cells after treatment with 10 lM latanoprost acid showed a statistically significant increase in expression; this increase was abrogated by cotreatment with a siRNA for FOXC1. CONCLUSIONS.We show the abrogation of latanoprost signalling when FOXC1 is knocked down via siRNA in a trabecular meshwork cell line. We propose that the lower levels of active FOXC1 in Axenfeld-Rieger syndrome patients with glaucoma account for the lack of response to prostaglandin-based medications.Keywords: prostaglandins, Glaucoma, latanoprost, Axenfeld-Rieger, FOXC1 G laucoma is a leading cause of blindness in developed nations and is caused by the death of retinal ganglion cells within the retina. It has been predicted that 79.6 million people will be affected by glaucoma by the year 2020, 10% of whom will be bilaterally blind.1 Risk factors for the development of glaucoma include corticosteroid use, smoking, age, and ethnicity.2 However, the major risk factor for glaucoma is an increase in intraocular pressure (IOP). Generation and maintenance of IOP occurs through aqueous humor (AH) flow. Outflow of AH occurs through two outflow facilities, conventional and uveoscleral, generating this IOP, which maintains the globular structure of the eye. As increased IOP is the major risk factor for developing glaucoma, it is also the primary target for medical intervention. To manage IOP, surgical or pharmaceutical interventions are employed to either increase AH outflow or to decrease the amount of AH produced. The most common treatment for glaucoma is the administration of prostaglandinbased medications to lower IOP through increasing flow via the uveoscleral outflow facility. This outflow occurs through the supraciliary...

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The expression and functional role of a FOXC1 related mRNA-lncRNA pair in oral squamous cell carcinoma

Cited by 58 publications

References 22 publications

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

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

Role of non‐coding RNAs in head and neck squamous cell carcinoma: A narrative review

FOXC1 Regulates Expression of Prostaglandin Receptors Leading to an Attenuated Response to Latanoprost

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