LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4

Niu, Yue; Wang, Gaoyan; Li, Yan; Guo, Wei; Guo, Yanli; Zhang, Dong

doi:10.3389/fonc.2021.773864

Cited by 11 publications

(6 citation statements)

References 60 publications

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“…showed that FOXP4-AS1 regulates the expression of FOXP4 positively by regulating miR-3184-5p in esophageal squamous cell carcinoma (ESCC) cells ( 18 ). Moreover, in Niu et al.’s study, they found a positive relation between FOXP4 and FOXP4-AS1 in ESCC ( 38 ). A positive association between FOXP4-AS1 and FOXP4 was also found in ovarian cancer (OC) tissues ( 25 ).…”

Section: Discussionmentioning

confidence: 89%

FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway

et al. 2022

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Papillary thyroid carcinoma, also known as PTC, is one of the commonest malignancies in the endocrine system. Long non-coding RNAs (lncRNAs) in PTC could maintain proliferative signaling, induce therapeutic resistance, activate invasion and migration, and sustain stem cell-like characteristics. In this paper, results showed that lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) is downregulated in PTC tissues and cell lines. Patients in TCGA cohort with a higher FOXP4-AS1 expression showed a higher disease-free interval (DFI) rate, and the expression of FOXP4-AS1 is shown to be linked to the clinical stage, T stage, N stage, and extraglandular invasion condition of the TC patients. FOXP4-AS1 is localized in the cell cytoplasmic domain of PTC cells. Functionally, upregulated FOXP4-AS1 inhibited PTC cell proliferation, apoptosis, and migration, whereas it downregulated FOXP4-AS1-promoted progression of PTC. In vivo assay also confirmed the tumor inhibitory effect of FOXP4-AS1 in PTC growth. Mechanism analysis indicated that FOXP4-AS1 can play its functions by regulating the AKT signaling pathway, and AKT inhibitor treatment could attenuate the impact of FOXP4-AS1 on PTC progression. Furthermore, FOXP4-AS1 also negatively regulates the expression of its host gene FOXP4. Collectively, we showed that FOXP4-AS1 inhibited PTC progression although AKT signaling and FOXP4-AS1 plays a tumor-suppressor role in PTC tumorigenesis.

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Section: Discussionmentioning

confidence: 89%

FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway

et al. 2022

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“…Recently, they have attracted attention as potential key layers of cancer cell regulation [ 8 , 25 ]. Meanwhile, increasing studies have revealed that lncRNAs exerted biological and clinical relevance of proliferation and metastasis-associated function in ESCC [ 26 – 28 ]. In the present study, we found that RPL34-AS1 was obviously downregulated in ESCC cells and tissues, and low RPL34-AS1 expression was associated with poor prognosis of EC patients.…”

Section: Discussionmentioning

confidence: 99%

LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis

Zhang

Pan²,

Zhang

et al. 2022

BMC Cancer

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Background Long noncoding RNAs (lncRNAs) are abnormally expressed in a broad type of cancers and play significant roles that regulate tumor development and metastasis. However, the pathological roles of lncRNAs in esophageal squamous cell carcinoma (ESCC) remain largely unknown. Here we aimed to investigate the role and regulatory mechanism of the novel lncRNA RPL34-AS1 in the development and progression of ESCC. Methods The expression level of RPL34-AS1 in ESCC tissues and cell lines was determined by RT-qPCR. Functional experiments in vitro and in vivo were employed to explore the effects of RPL34-AS1 on tumor growth in ESCC cells. Mechanistically, fluorescence in situ hybridization (FISH), bioinformatics analyses, luciferase reporter assay, RNA immunoprecipitation (RIP) assay and western blot assays were used to detect the regulatory relationship between RPL34-AS1, miR-575 and ACAA2. Results RPL34-AS1 was significantly down-regulated in ESCC tissues and cells, which was negatively correlated with overall survival in ESCC patients. Functionally, upregulation of RPL34-AS1 dramatically suppressed ESCC cell proliferation, colony formation, invasion and migration in vitro, whereas knockdown of RPL34-AS1 elicited the opposite function. Consistently, overexpression of RPL34-AS1 inhibited tumor growth in vivo. Mechanistically, RPL34-AS1 acted as a competing endogenous RNA (ceRNA) of miR-575 to relieve the repressive effect of miR-575 on its target ACAA2, then suppressed the tumorigenesis of ESCC. Conclusions Our results reveal a role for RPL34-AS1 in ESCC tumorigenesis and may provide a strategy for using RPL34-AS1 as a potential biomarker and an effect target for patients with ESCC.

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“…[ 23 ] Niu et al,s research found that lncRNA FOXP4-AS1, which is upregulated in esophageal squamous cell carcinoma (ESCC), promotes FOXP4 expression by enriching MLL2 and H3K4me3 in the FOXP4 promoter through a “molecular scaffold.” Moreover, FOXP4, a transcription factor of β-catenin, promotes the transcription of β-catenin and ultimately leads to malignant progression of ESCC. [ 24 ] Liu et al found that lncRNA FOXP4-AS1 may function in pancreatic ductal adenocarcinoma (PDAC) by participating in biological processes and pathways, including oxidative phosphorylation, tricarboxylic acid cycle, and classical tumor-related pathways such as NF-kappaB and Janus kinase/signal transducers, in addition to activators of transcription, cell proliferation, and adhesion. [ 25 ] Activation of DNA repair is one of the reasons for chemoresistance, and the myc-pathway has been associated with the acquisition of temozolomide resistance in glioblastoma through a c-Myc–miR-29c–REV3L network.…”

Section: Discussionmentioning

confidence: 99%

The clinical prognostic value of lncRNA FOXP4-AS1 in cancer patients: A meta-analysis and bioinformatics analysis based on TCGA datasets

Shu¹,

Liu²,

Yang³

et al. 2022

Medicine

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Background: The mortality and recurrence of patients with cancer is of high prevalence. Long non-coding RNA (lncRNA) forkhead box P4 antisense RNA 1 (FOXP4-AS1) is a promising lncRNA. There is increasing evidence that lncRNA FOXP4-AS1 is abnormally expressed in various tumors and is associated with cancer prognosis. This study was designed to identify the prognostic value of lncRNA FOXP4-AS1 in human malignancies. Methods: We searched electronic databases up to April 29, 2022, including PubMed, Cochrane Library, Embase, MEDLINE, and Web of Science. Eligible studies that evaluated the clinicopathological and prognostic role of lncRNA FOXP4-AS1 in patients with malignant tumors were included. The pooled odds ratios (ORs) and the hazard ratios (HRs) were calculated to assess the role of lncRNA FOXP4-AS1 using Stata/SE 16.1 software. Results: A total of 6 studies on cancer patients were included in the present meta-analysis. The combined results revealed that high expression of lncRNA FOXP4-AS1 was significantly associated with unfavorable overall survival (OS) (HR = 1.99, 95% confidence interval [CI]: 1.65–2.39, P < .00001), and poor disease-free survival (DFS) (HR = 1.81, 95% CI: 1.54–2.13, P < .00001) in a variety of cancers. In additional, the increase in lncRNA FOXP4-AS1 expression was also correlated with tumor size ((larger vs smaller) (OR = 3.16, 95% CI: 2.12–4.71, P < .00001), alpha-fetoprotein (≥400 vs <400) (OR = 3.81, 95%CI: 2.38–6.11, P = .83), lymph node metastasis (positive vs negative) (OR = 2.93, 95%CI: 1.51–5.68, P = .001), and age (younger vs older) (OR = 2.06, 95% CI: 1.41–3.00, P = .00002) in patients with cancer. Furthermore, analysis results using The Cancer Genome Atlas (TCGA) dataset showed that the expression level of lncRNA FOXP4-AS1 was higher in most tumor tissues than in the corresponding normal tissues, which predicted a worse prognosis. Conclusions: In this meta-analysis, we demonstrate that high lncRNA FOXP4-AS1 expression may become a potential marker to predict cancer prognosis.

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LncRNA FOXP4-AS1 Promotes the Progression of Esophageal Squamous Cell Carcinoma by Interacting With MLL2/H3K4me3 to Upregulate FOXP4

Cited by 11 publications

References 60 publications

FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway

FOXP4-AS1 Inhibits Papillary Thyroid Carcinoma Proliferation and Migration Through the AKT Signaling Pathway

LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis

The clinical prognostic value of lncRNA FOXP4-AS1 in cancer patients: A meta-analysis and bioinformatics analysis based on TCGA datasets

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