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Although lncRNAs are recognized to contribute to the development of oral squamous-cell carcinoma (OSCC), their exact function in invasion and cell migration is not clear. In this research, we explored the molecular and cellular mechanisms of FOXD2-AS1 in OSCC. Prognostic and bioinformatics analyses were used to test for the differential expression of FOXD2-AS1-PLOD1. Following FOXD2-AS1 suppression or overexpression, changes in cell viability were measured using the CCK-8 test; changes in cell migration and invasion abilities were measured using the migration and the Transwell assay. The expression of associated genes and proteins was found using Western blot and RT-qPCR. Analysis of luciferase reporter genes was done to look for regulatory connections between various molecules. The FOXD2-AS1-PLOD1 pair, which was highly expressed in OSCC, was analyzed and experimentally verified to be closely related to the prognosis of OSCC, and a nomogram model and correction curve were constructed. The inhibition of FOXD2-AS1 resulted in the reduction of cell activity, migration, invasion ability and changes in genes related to invasion and migration. In vivo validation showed that inhibition of FOXD2-AS1 expression slowed tumor growth, and related proteins changed accordingly. The experiments verified that FOXD2-AS1 negatively regulated miR-185-5 p and that miR-185-5 p negatively regulated PLOD1. In addition, it was found that the expression of PLOD1, p-Akt and p-mTOR proteins in OSCC cells was reduced by the inhibition of FOXD2-AS1, and FOXD2-AS1 and PLOD1 were closely related to the Akt/mTOR pathway. Increased expression of FOXD2-AS1 promotes OSCC growth, invasion and migration, which is important in part by targeting miR-185-5 p/PLOD1/Akt/mTOR pathway activity.
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Movimiento Celular , Proliferación Celular , MicroARNs , Neoplasias de la Boca , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-akt , ARN Largo no Codificante , Serina-Treonina Quinasas TOR , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Movimiento Celular/genética , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Proliferación Celular/genética , Ratones , Animales , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/genética , Procolágeno-Lisina 2-Oxoglutarato 5-Dioxigenasa/metabolismo , Línea Celular Tumoral , Transducción de Señal/genética , Regulación Neoplásica de la Expresión Génica , Femenino , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Masculino , Pronóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Ratones DesnudosRESUMEN
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with an unfavorable outcome. The present research aimed to identify novel biological targets for AML diagnosis and treatment. In this study, we performed an in-silico method to identify antisense RNAs (AS-RNAs) and their related co-expression genes. GSE68172 was selected from the AML database of the Gene Expression Omnibus and compared using the GEO2R tool to find DEGs. Antisense RNAs were selected from all the genes that had significant expression and a survival plot was drawn for them in the GEPIA database, FOXD2-AS1 was chosen for further investigation based on predetermined criteria (logFC ≥|1| and P < 0.05) and its noteworthy association between elevated expression level and a marked reduction in the overall survival (OS) in patients diagnosed with AML. The GEPIA database was utilized to investigate FOXD2-AS1-related co-expression and similar genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) function analysis of the mentioned gene lists were performed using the DAVID database. The protein-protein interaction (PPI) network was then constructed using the STRING database. Hub genes were screened using Cytoscape software. Pearson correlation analysis was conducted using the GEPIA database to explore the relationship between FOXD2-AS1 and the hub genes. The transcription of the selected coding and non-coding genes, including FOXD2-AS1, CDC45, CDC20, CDK1, and CCNB1, was validated in 150 samples, including 100 primary AML non-M3 blood samples and 50 granulocyte colony stimulating factor (G-CSF)-mobilized healthy donors, using quantitative Real-Time PCR (qRT-PCR). qRT-PCR results displayed significant upregulation of lnc-FOXD2-AS1, CDC45, and CDK1 in primary AML non-M3 blood samples compared to healthy blood samples (P = 0.0032, P = 0.0078, and P = 0.0117, respectively). The expression levels of CDC20 and CCNB1 were not statistically different between the two sets of samples (P = 0.8315 and P = 0.2788, respectively). We identified that AML patients with upregulation of FOXD2-AS1, CDK1, and CDC45 had shorter overall survival (OS) and Relapse-free survival (RFS) compared those with low expression of FOXD2-AS1, CDK1, and CDC45. Furthermore, the receiver operating characteristic (ROC) curve showed the potential biomarkers of lnc -FOXD2-AS1, CDC45, and CDK1 in primary AML non-M3 blood samples. This research proposed that the dysregulation of lnc-FOXD2-AS1, CDC45, and CDK1 can contribute to both disease state and diagnosis as well as treatment. The present study proposes the future evolution of the functional role of lnc-FOXD2-AS1, CDC45, and CDK1 in AML development.
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FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is a long non-coding RNA being transcribed from a locus on chromosome 1p33. This transcript has been found to be up-regulated in tumor samples of almost all types of malignancies in association with a significant increase in malignant features. FOXD2-AS1 can affect activity of PI3K/AKT, AKT/mTOR, Hippo/YAP, Notch, NRf2, Wnt/ß-catenin, NF-ÆB and ERK/MAPK pathways. Furthermore, it can enhance stem cell properties in cancer cells and prompt epithelial-mesenchymal transition. It is also involved in induction of resistance to a variety of anticancer agents such as adriamycin, cisplatin, 5-fluorouracil, temozolomide and gemcitabine. This article summarizes the impact of FOXD2-AS1 in diverse human disorders.
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MicroARNs , ARN Largo no Codificante , Humanos , Línea Celular Tumoral , Proliferación Celular/genética , Cisplatino , Gemcitabina , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Objective To investigate the relationship between the expression of long non-coding RNA HOXA-AS2(lncRNA HOXA-AS2),long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1),and long non-coding RNA CRNDE(lncRNA CRNDE)in endometrial carcinoma and the clinical pathological character-istics and prognosis of patients.Methods Collect samples of endometrial carcinoma cancer tissues and adja-cent tissues excised during surgery from 119 endometrial carcinoma patients admitted to a hospital from Octo-ber 2017 to February 2020.The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in tissues were retrospectively analyzed,as well as their relationship with clinicopathological features and 3-year survival rate of patients.Results The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were higher than those in adjacent tissues,with statistical signifi-cance(P＜0.05).The relative expression levels of HOXA-AS2,FOXD2-AS1 and CRNDE in cancer tissues of endometrial carcinoma patients were positively correlated(rHOXA-As2 vs.FOXD2-AS1=0.384,P=0.001;rHoXA-AS2 vs.CRNDE=0.576,P＜0.001;rFoXD2-AS1 vs.CRNDE=0.326,P=0.003).In the HOXA-AS2,FOXD2-AS1 and CRNDE high expression group,the proportion of patients with international federation of gynecology and ob-stetrics(FIGO)stage Ⅲ+Ⅳ,lymph node metastasis,deep infiltration and low differentiation was higher than that in the low expression group,with statistical significance(P＜0.05).The 3-year survival rate of low HOXA-AS2 expression group in endometrial cancer patients(52/60,86.67％)was higher than that of high HOXA-AS2 expression group(40/59,67.79％),the difference was statistically significant(x2=6.039,P＜0.05).The 3-year survival rate of patients with endometrial cancer with low FOXD2-AS1 expression group(53/59,89.83％)was higher than that of patients with endometrial cancer with high FOXD2-AS1 expression group(39/60,65.00％),and the difference was statistically significant(x2=10.456,P＜0.05).The 3-year sur-vival rate of low CRNDE expression group in endometrial cancer patients(51/60,85.00％)was higher than that of high CRNDE expression group(41/59,69.49％),and the difference was statistically significant(x2=4.079,P＜0.05).HOXA-AS2,FOXD2-AS1,and CRNDE were risk factors for death in endometrial carcinoma patients(P＜0.05).Conclusion The expression of HOXA-AS2,FOXD2-AS1,and CRNDE in endometrial carcinoma cancer tissue is closely related to the clinical pathological characteristics and prognosis of patients.
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Achilles tendinopathy is a prevalent clinical problem that plagues athletes and general populations. Achilles tendon healing is a complex process, and so far, there is no successful long-term solution to Achilles tendinopathy in the field of microsurgery due to its poor natural regeneration ability. Limitations in understanding the pathogenesis of Achilles tendon development and Achilles tendon injury hinder clinical treatment developments. There is an increasing demand for innovative conservative treatments that can improve Achilles tendon injury. In this study, a Sprague-Dawley rat model of Achilles tendinopathy was established. Lentiviral vectors that interfere with the expression of FOXD2-AS1, miR-21-3p, or PTEN were injected every 3 days. Rats were euthanized after 3 weeks, and the effect of FOXD2-AS1, miR-21-3p, or PTEN on Achilles tendon healing was analyzed by histological observation, biomechanical test, and examinations of inflammatory factors and tendon markers. As measured, downregulating FOXD2-AS1 or upregulating miR-21-3p improved histological structure, suppressed inflammation, promoted the expression of tendon markers, and optimized the biomechanical properties of Achilles tendon. Upregulating PTEN was capable of reversing the promoting effect of inhibition of FOXD2-AS1 on Achilles tendon healing. As concluded, deficiency of FOXD2-AS1 accelerates the healing of Achilles tendon injury and improves tendon degeneration by regulating the miR-21-3p/PTEN axis and promoting the activation of the PI3K/AKT signaling pathway.
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Tendón Calcáneo , MicroARNs , ARN Largo no Codificante , Tendinopatía , Ratas , Animales , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Tendón Calcáneo/metabolismo , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas Sprague-Dawley , Tendinopatía/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Background: Long non-coding RNA FOXD2 antisense RNA 1 (FOXD2-AS1) has been reported in many malignancies. However, the molecular mechanism of many actions is not clarified. This study was conducted to investigate the function of FOXD2-AS1 in lung adenocarcinoma and its molecular mechanism. Methods: Bioinformatics and in vitro analysis including RT-qPCR, CFU, CCK8, Transwell, Cell Apoptosis and Cell Cycle Assay were used for the analysis of gene expression and related effects. Results: It revealed increased expression of lncRNA FOXD2-AS1 in lung adenocarcinoma cell lines (A549 cells), and abundant expression of lncRNA FOXD2-AS1 was also observed in the acquired lung adenocarcinoma tissues. In vitro results showed that knockdown of lncRNA FOXD2-AS1 in A549 cells weakened cell proliferation, invasion and increased apoptosis. At the same time, we found that reducing the expression of lncRNA FOXD2-AS1 caused cell cycle arrest in the G1/S phase. Differential gene analysis of lung adenocarcinoma and adjacent normal tissues showed that the cell cycle and its related process regulation were significantly enriched. Gene Set Enrichment Analysis (GSEA) analysis showed that miR-206, miR-143, lL6-JAK-STAT3 signalling pathway, STAT3, E2F targets, EZH2, P53 signalling pathway and E2F3 targets interacting with lncRNA FOXD2-AS1 were also enriched. Conclusion: This study demonstrates the role and mechanism of the lncRNA FOXD2-AS1 in lung adenocarcinoma and provides a better understanding for the treatment of lung adenocarcinoma, which indicates that interfering with lncRNA FOXD2-AS1 expression may be a novel strategy.
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The healing of skin wounds is a highly coordinated multi-step process that occurs after trauma including surgical incisions, thermal burns, and chronic ulcers. In this study, the authors investigated lncRNA FOXD2-AS1 function in adipose mesenchymal exosomes from ADMSCs that were successfully extracted. Highly expressed lncRNA FOXD2-AS1 in ADMSCs-exosomes accelerated HaCaT cell migration and proliferation. LncRNA FOXD2-AS1 negatively targeted miR-185-5p, and miR-185-5p negatively targeted ROCK2. Highly expressed lncRNA FOXD2-AS1 in ADMSCs-exosomes promoted HaCaT cell migration and proliferation via down-regulating miR-185-5p and further up-regulating ROCK2. In conclusion, LncRNA FOXD2-AS1 overexpression in ADMSCs derived exosomes might accelerate HaCaT cell migration and proliferation via modulating the miR-185-5p/ROCK2 axis.
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Exosomas , Células Madre Mesenquimatosas , MicroARNs , ARN Largo no Codificante , Quinasas Asociadas a rho , Humanos , Células HaCaT , MicroARNs/genética , ARN Largo no Codificante/genéticaRESUMEN
AIM: We have previously characterized oncogenic properties of IGF2BP1 in HCC, and its regulation by short noncoding RNAs (ncRNAs). Recent evidence suggests that IGF2BP1 itself may regulate long ncRNAs (lncRNAs). Therefore, this study aimed at exploring the interplay between IGF2BP1 and various upstream and downstream ncRNAs and its link to HCC pathogenesis. MATERIALS AND METHODS: Bioinformatic analysis was used to identify up- and downstream ncRNAs interacting with IGF2BP1. Huh-7 cells were transfected with siRNAs against IGF2BP1 and microRNA mimics. Relative gene expression was determined using RTqPCR and IGF2BP1 protein was quantified by western blot. Luciferase binding assay was used to explore the targeting of IGF2BP1 3'UTR. HCC tumorigenesis was measured by MTT assay, BrdU-incorporation assay, colony-forming assay, and scratch assay. KEY FINDINGS: Bioinformatic analysis identified three oncogenic lncRNAs - namely H19, FOXD2-AS1, and SNHG3 - potentially regulated by IGF2BP1. Knockdown of IGF2BP1 decreased the expression of all three oncogenic lncRNAs and inhibited malignant cell behaviors. miR-186 was revealed as a possible upstream regulator of IGF2BP1. miR-186 mimics decreased IGF2BP1 mRNA and protein levels. miR-186 was significantly lower while IGF2BP1 was elevated in cancerous tissues from ten HCC patients compared to five healthy controls. In addition, miR-186 mimics caused a downregulation of the oncogenic lncRNAs H19, SNHG3, and FOXD2-AS1 and a concomitant decrease in cell viability, proliferation, migration, and clonogenicity. SIGNIFICANCE: miR-186 may exert tumor suppressor effects in HCC by repressing oncogenic lncRNAs H19, SNHG3, and FOXD2-AS1 through its effect on IGF2BP1.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , ARN Largo no Codificante , Proteínas de Unión al ARN , Humanos , Carcinogénesis/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismoRESUMEN
Purpose: A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines.MethodsThe biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay.ResultsThrough bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth.ConclusionsIn general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients. (AU)
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Humanos , Línea Celular Tumoral , Proliferación Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Regulación Neoplásica de la Expresión Génica , Oncogenes , MicroARNs , ARN Largo no CodificanteRESUMEN
PURPOSE: A growing number of evidences has revealed that long non-coding RNAs (lncRNAs) have vital effect in the pathogenesis of esophageal squamous cell carcinoma (ESCC). In our work, we found that lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) was significantly increased in clinical ESCC samples and cell lines. METHODS: The biological effect of FOXD2-AS1 on EC109 and KYSE150 cells showed that the low expression of FOXD2-AS1 inhibited the proliferation through CCK8 and colony formation assays, invasion by transwell chamber test, migration abilities by wound healing assay, and enhance apoptosis rates by flow cytometry assay. RESULTS: Through bioinformatics analysis and luciferase reporter assays, microRNA (miR)-204-3p was proved to be a target of FOXD2-AS1. We further confirmed that FOXD2-AS1 was the upstream inhibitor of miR-204-3p and the down-regulation of miR-204-3p reversed the repressive effects of low expression of FOXD2-AS1 on ESCC progression. In addition, inhibition of FOXD2-AS1 effectively suppressed the tumor growth. CONCLUSIONS: In general, our results suggested that FOXD2-AS1 may be of vital therapeutic importance for the treatment of ESCC patients.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , MicroARNs , ARN Largo no Codificante , Línea Celular Tumoral , Proliferación Celular , Carcinoma de Células Escamosas de Esófago/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Oncogenes , ARN Largo no Codificante/genéticaRESUMEN
Emerging data have highlighted the importance of long noncoding RNAs (lncRNAs) in exerting critical biological functions and roles in different forms of brain cancer, including gliomas. In this study, we sought to investigate the role of lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) in glioma cells. First, we used sphere formation assay and flow cytometry to select U251 glioma stem cells (GSCs). Then, we quantified the expression of lncRNA FOXD2-AS1, TATA-box binding protein associated factor 1 (TAF-1) and NOTCH1 in glioma tissues and GSCs, as well as the expression of GSC stem markers, OCT4, SOX2, Nanog, Nestin and CD133 in GSCs. Colony formation assay, sphere formation assay, and flow cytometry were used to evaluate GSC stemness. Next, the correlations among lncRNA FOXD2-AS1, TAF-1 and NOTCH1 were investigated. LncRNA FOXD2-AS1, TAF-1 and NOTCH1 were found to be elevated in glioma tissues and GSCs, and silencing lncRNA FOXD2-AS1 inhibited stemness and proliferation, while promoting apoptosis and differentiation of GSCs. LncRNA FOXD2-AS1 overexpression also led to increased NOTCH1 by recruiting TAF-1 to the NOTCH1 promoter region, thereby promoting stemness and proliferation, while impairing cell apoptosis and differentiation. Mechanistically, lncRNA FOXD2-AS1 elevation promoted glioma in vivo by activating the NOTCH signalling pathway via TAF-1 upregulation. Taken together, the key findings of our investigation support the proposition that downregulation of lncRNA FOXD2-AS1 presents a viable and novel molecular candidate for improving glioma treatment.
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Glioma , MicroARNs , ARN Largo no Codificante , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Glioma/genética , Glioma/metabolismo , Humanos , MicroARNs/genética , Células Madre Neoplásicas/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Long noncoding RNAs (lncRNAs) play critical roles in tumor progression regulation, including osteosarcoma. Evidence indicates that N6-methyladenosine (m6A) modification modulates mRNA stability to regulate osteosarcoma tumorigenesis. Here, present research aims to detect the roles of m6A-modified lncRNA FOXD2-AS1 in the osteosarcoma pathophysiological process. Clinical data unveiled that osteosarcoma patients with higher FOXD2-AS1 expression had a poorer overall survival rate compared to those with lower FOXD2-AS1 expression. Functional research illuminated that FOXD2-AS1 accelerated the migration, proliferation and tumor growth in vitro and in vivo. Mechanistically, a remarkable m6A-modified site was found on the 3'-UTR of FOXD2-AS1, and m6A methyltransferase WTAP (Wilms' tumor 1 associated protein) promoted the methylation modification, thus enhancing the stability of FOXD2-AS1 transcripts. Furthermore, FOXD2-AS1 interacted with downstream target FOXM1 mRNA through m6A sites, forming a FOXD2-AS1/m6A/FOXM1 complex to heighten FOXM1 mRNA stability. In conclusion, these findings propose a novel regulatory mechanism in which m6A-modified FOXD2-AS1 accelerates the osteosarcoma progression through m6A manner, which may provide new concepts for osteosarcoma tumorigenesis.
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Neoplasias Óseas , Osteosarcoma , ARN Largo no Codificante , Regiones no Traducidas 3' , Adenosina/análogos & derivados , Neoplasias Óseas/genética , Carcinogénesis/genética , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Proteína Forkhead Box M1/genética , Proteína Forkhead Box M1/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Metiltransferasas/genética , Metiltransferasas/metabolismo , Osteosarcoma/genética , Osteosarcoma/patología , Factores de Empalme de ARN/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Long noncoding RNA FOXD2 adjacent opposite strand RNA1 (FOXD2-AS1) plays an oncogenic role in various cancers, including gastric cancer (GC). However, the function of FOXD2-AS1 in regulating radiosensitivity of GC cells and its underlying molecular mechanisms have not been elucidated. This study aimed to figure out the potential mechanisms of FOXD2-AS1 in regulating GC cell radiosensitivity. RT-qPCR revealed upregulation of FOXD2-AS1 in GC cells exposed to radiation. Subcellular fractionation assay was used to localize FOXD2-AS1 in GC cells. Colony formation, MTT, EdU, and flow cytometry assays were performed to investigate the role of FOXD2-AS1 in regulating cell proliferation, cell cycle progression, and cell apoptosis. Western blotting was used to assess protein levels of apoptosis-associated markers and SET domain containing 1A (SETD1A). Homologous recombination reporter assay was conducted to explore the effect of FOXD2-AS1 on DNA damage repair. The downstream molecules of FOXD2-AS1 were identified with RNA pulldown, luciferase reporter, and RNA immunoprecipitation assays. The results showed that FOXD2-AS1 knockdown suppressed cell proliferation and cell cycle progression and promoted cell apoptosis and radiosensitivity of GC. FOXD2-AS1 could bind with miR-1913 in GC cells. In addition, miR-1913 targeted SETD1A, which was highly expressed in GC cells. Overexpression of SETD1A reversed FOXD2-AS1 silencing-induced effects on proliferation, apoptosis, and radiosensitivity of GC cells. In conclusion, knocking down FOXD2-AS1 enhances the radiosensitivity of GC cells by sponging miR-1913 to upregulate SETD1A expression.
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MicroARNs , ARN Largo no Codificante , Neoplasias Gástricas , Línea Celular Tumoral , Proliferación Celular/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica/genética , N-Metiltransferasa de Histona-Lisina/genética , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Tolerancia a Radiación/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/radioterapiaRESUMEN
BACKGROUND: Long non-coding RNA (lncRNA) has been testified to influence the initiation and evolution of sundry carcinomas. Recently, lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) has been found to display vital regulating functions in various cancers. METHODS: qRT-PCR was used to verify the dysregulation of FOXD2-AS1 expression in CCA cells and tissues, and the correlation of FOXD2-AS1 expression with clinicopathological characteristics was investigated. The viability, migration, and invasion of CCA cells were verified through CCK-8 assay, colony formation experiment, wound healing assay, and transwell assay. The regulatory networks of FOXD2-AS1 were analyzed by Bioinformatic prediction and dual-luciferase reporter assay. RESULTS: We discovered that FOXD2-AS1 was significantly upregulated in CCA and its up-regulation was closely correlated with terminal TNM stage, lymph node metastasis and poor survival in the current research. In addition, it was revealed that FOXD2-AS1 was an independent prognostic factor. Functional tests uncovered that the cell viability, migration, and invasion could be restrained through downregulating the expression of FOXD2-AS1, while FOXD2-AS1 overexpression could facilitate the cell viability, migration, and invasion. Mechanistically, FOXD2-AS1 was founded to interact directly with miR-760 and the oncogene E2F3 was the downstream target of miR-760 through bioinformatic prediction and dual-luciferase reporter assays. Finally, we testified that FOXD2-AS1 could competitively sponge miR-760 and further upregulated the E2F3 expression to play a vital part in cholangiocarcinoma. CONCLUSIONS: This research revealed that lncRNA FOXD2-AS1 could enhance CCA malignant progression through regulating the miR-760/E2F3 axis and was expected to be a prognostic biomarker and therapeutic target for cholangiocarcinoma.
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Neoplasias de los Conductos Biliares/genética , Proliferación Celular/genética , Colangiocarcinoma/genética , Factor de Transcripción E2F3/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Neoplasias de los Conductos Biliares/patología , Movimiento Celular/genética , Colangiocarcinoma/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Invasividad NeoplásicaRESUMEN
PURPOSE: Gastric cancer (GC) is one of the most frequent tumors worldwide and identification of a sensitive and specific prognostic biomarker is of great importance. Long non-coding RNAs (lncRNAs) play crucial roles in tumorigenesis of various malignancies. In the present study, we investigated lncRNA FOXD2-AS1 expression in gastric tumors and assessed its potential as a prognostic biomarker. METHODS: A total of 95 tumor and corresponding adjacent non-tumor tissue specimens were collected from patients with GC from Imam Reza hospital, Tabriz, Iran. Total RNA was isolated and FOXD2-AS1 expression was measured using quantitative reverse transcriptase (qRT)-PCR. RESULTS: FOXD2-AS1 was significantly upregulated in tumor samples as compared to non-tumor tissues (P < 0.0001). In addition, higher expression of FOXD2-AS1 was significantly associated with lymph node metastasis and Helicobacter pylori infection. The receiver operating characteristic (ROC) curve analysis revealed that FOXD2-AS1 might be served as a potential prognostic biomarker for GC. CONCLUSION: FOXD2-AS1 is upregulated in gastric tumors and can be used as a valuable biomarker in the prognosis of patients with GC.
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Infecciones por Helicobacter , Helicobacter pylori , ARN Largo no Codificante , Neoplasias Gástricas , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Helicobacter pylori/genética , Humanos , Pronóstico , ARN Largo no Codificante/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
Background: Colorectal cancer (CRC) is still considered one of the prevalent cancers worldwide. Investigation of potential biomarkers for early detection of CRC is essential for the effective management of patients using therapeutic strategies. Considering that, this study was aimed to examine the changes in lncRNA FOXD2-AS1 expression through colorectal tumorigenesis. Methods: Fifty CRC tumor tissues and fifty adjacent normal tissue samples were prepared and involved in the current study. Total RNA was extracted from the samples and then reverse transcribed to complementary DNA. Next, the expression levels of lncRNA FOXD2-AS1 were evaluated using real-time PCR in CRC samples compared to normal ones. Also, receiver operating characteristic curve analysis was used to evaluate the diagnostic value of FOXD2-AS1 for CRC. Results: The obtained results showed that the expression level of FOXD2-AS1 gene was significantly (p<0.0001) up-regulated in tumor tissues compared to normal marginal tissues. Also, a significant correlation was observed between higher the expression of FOXD2-AS1and the differentiation of tumor cells. Furthermore, ROC curve analysis estimated an AUC value of 0.59 for FOXD2-AS1, suggesting its potential as a diagnostic target. Conclusion: Taken together, the current study implied that tissue-specific upregulation of lncRNA FOXD2-AS1 might be appropriate diagnostic biomarkers for CRC. Nonetheless, more studies are needed to validate these results and further illustrate FOXD2-AS1 function through colorectal tumorigenesis.
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Recent studies have indicated that long noncoding RNA (lncRNA) and N6-methyladenosine (m6A) methylation modification play critical roles in human cancers; however, their regulation on cervical cancer is largely unclear. Here, our study tries to investigate the underlying mechanisms by which lncRNA FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) modulates cervical cancer tumorigenesis. Results illuminated that FOXD2-AS1 expression was significantly upregulated in cervical cancer cells and tissue, which was closely correlated to the unfavorable prognosis. Functionally, gain and loss-of-function assays showed that FOXD2-AS1 promoted the migration and proliferation of cervical cancer cells. Besides, FOXD2-AS1 silencing repressed the tumor growth in vivo. Mechanistically, m6A methyltransferase methyltransferase-like 3 (METTL3) enhanced the stability of FOXD2-AS1 and maintained its expression. Moreover, FOXD2-AS1 recruited lysine-specific demethylase 1 (LSD1) to the promoter region of p21 to silence its transcription abundance. In conclusion, these findings support that METTL3/FOXD2-AS1 accelerates cervical cancer progression via a m6A-dependent modality, which may serve as a potential therapeutic target for cervical cancer.
RESUMEN
BACKGROUND: The aim of this study is to summarize the current findings concerning the FOXD2-AS1 expression and cancer prognosis. METHODS: The correlation intensity between FOXD2-AS1 expression and cancer prognosis was estimated using pooled hazard ratio (HRs) with 95% confidence intervals (CIs). GEPIA was used to assess disease-free survival (DFS), progression-free survival (PFS) and overall survival (OS) of cancer patients and differential FOXD2-AS1 expression in cancer and adjacent tissues. RESULTS: A total of 11 studies including 2,177 patients with OS and 477 patients with DFS/PFS data were analyzed in evidence synthesis. Overall, the pooled analysis indicated that FOXD2-AS1 expression was significantly associated with OS (HR=1.51, 95%Cl: 1.26-1.81, P<0.001) and DFS (HR=1.66, 95%CI: 1.34-2.04, P<0.001). Subgroup analysis showed that high expression of FOXD2-AS1 was significant correlated with poor OS in the median (HR=1.51, 95%CI: 1.30-1.75, P<0.001) and normal group (HR=1.50, 95%CI: 1.09-2.05, 0.01) based on cut-off value, and high FOXD2-AS1 expression was significant linked with poor DFS in patients with digestive tract cancer (DTC) (HR=1.66, 95%CI: 1.34-2.04, P<0.001). Similarly, a significant correlation between increased FOXD2-AS1 expression and poor PFS with other cancers (HR=3.84, 95%CI 1.26-11.70, P=0.02) was found. In database testing, a highly significant correlation was observed between high expression of FOXD2-AS1 and poor OS (HR=1.9, P<0.001), but not DFS (HR=1.0, P=0.900). CONCLUSIONS: Our findings indicated that FOXD2-AS1 may serve as a potential independent prognostic factor in cancer, especially in the Chinese population.
Asunto(s)
Biomarcadores de Tumor/genética , Bases de Datos Genéticas , ARN Largo no Codificante/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , ARN Largo no Codificante/genéticaRESUMEN
Numerous studies have demonstrated that lncRNAs participate in regulatory networks of different cancers. Dysregulation of various lncRNAs such as DUXAP8, LINC00963, and FOXD2-AS1 has been reported in the development of various cancers. The aim of this study was investigation of the importance and potential roles of DUXAP8, LINC00963, and FOXD2-AS1 in ER+ breast cancer (BC). We examined the expression levels of DUXAP8, LINC00963, and FOXD2-AS1 in 71 luminal A and B tumor tissues and two luminal A cell lines (MCF7 and T47D) compared with adjacent non-tumor tissues and MCF10A cell line by qRT-PCR assay, respectively. For identifying the relation between three lncRNAs and luminal BC, bioinformatic analyses were performed using some databases and software including GENEVESTIGATOR software, GEPIA2, DAVID, REVIGO, STRING, lncATLAS, Kaplan-Meier plotter, starBase, and miRNet tool. The results showed the significant upregulation of all three lncRNAs in luminal A and B tumor specimens and cell lines. Upregulation of DUXAP8 and FOXD2-AS1 was significantly associated with progesterone receptor-positive (PR+) and p53 protein expression in luminal BC patients, respectively. Based on bioinformatic analyses, DUXAP8 can be considered as a prognostic biomarker for patients with luminal BC. DUXAP8, LINC00963, and FOXD2-AS1 are involved in several cancer-associated signaling pathways and multiple cancer-related processes. In addition, bioinformatic analyses indicated that LINC00963/hsa-mir-130a-3p/HSPA8 axis might have potential regulatory role in BC. In conclusion, dysregulation of DUXAP8, LINC00963, and FOXD2-AS1 can play roles in the development of luminal BC. They may exert their functions through involvement in some cancer signaling pathways and processes. In addition, they may interact with miRNAs like predicted interaction of LINC00963 with miR-130a-3p.