LncRNA WWOX-AS1 sponges miR-20b-5p in hepatocellular carcinoma and represses its progression by upregulating WWOX.
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ABSTRACT:
SUBMITTER: Xu D
PROVIDER: S-EPMC7583509 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:In this study, we investigated the functional and clinical significance of the long non-coding RNA (lncRNA) FAM181A-AS1 in human gliomas. TCGA, GTEx and CGGA database analyses showed that high FAM181A-AS1 expression correlates with advanced tumor stage and poor survival of glioma patients. FAM181A-AS1 expression is higher in glioma cell lines compared to normal human astrocytes (NHA). CCK-8, EdU, and colony formation assays show that FAM181A-AS1 knockdown decreases proliferation and colony formation in glioma cells, whereas, FAM181A-AS1 overexpression reverses these effects. Bioinformatics analysis showed that miR-129-5p is a potential target of FAM181A-AS1. MiR-129-5p expression negatively correlates with FAM181A-AS1 expression in glioma patients. Dual luciferase reporter assays confirmed that miR-129-5p binds directly to FAM181A-AS1 in glioma cells. RNA immunoprecipitation (RIP) assays using anti-Ago2 antibody pulled down FAM181A-AS1 with miR-129-5p. Bioinformatics analysis identified ZRANB2 as a potential miR-129-5p target gene. Dual luciferase reporter assays confirmed that miR-129-5p binds directly to the 3'-UTR of ZRANB2 mRNA. Furthermore, miR-129-5p overexpression or ZRANB2 knockdown reduces proliferation and colony formation of FAM181A-AS1 overexpressing glioma cells. These findings show that FAM181A-AS1 promotes gliomagenesis by enhancing ZRANB2 expression by sponging of miR-129-5p.
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Project description:Increasing evidence has shown that circular RNAs (circRNAs) play critical roles in various diseases, including keloid. The purpose of this study was to investigate the role of circ_0057452 and related action mechanisms during the development of keloid. The expression levels of circ_0057452, microRNA-7-5p (miR-7-5p) and GRB2 associated binding protein 1 (GAB1) mRNA were determined by quantitative real-time PCR (qRT-PCR). Cell proliferation was evaluated using methylthiazolyldiphenyl-tetrazolium bromide (MTT) and 5-Ethynyl-2'-deoxyuridine (Edu) assays. Flow cytometry analysis was utilized to determine cell cycle distribution and cell apoptosis. Western blot assay was used to measure apoptosis-related, collagen synthesis-related, and GAB1 protein levels. Cell migration and invasion were detected by wound healing assay and transwell assay. The interaction between miR-7-5p and circ_0057452 or GAB1 was confirmed by dual-luciferase reporter, RNA pull-down, and RNA Immunoprecipitation (RIP) assays. Circ_0057452 and GAB1 were upregulated in keloid tissues and keloid fibroblasts (KFs), while miR-7-5p was downregulated. Circ_0057452 knockdown or miR-7-5p overexpression inhibited the proliferation, migration, invasion, and collagen synthesis and induced cell cycle arrest and apoptosis of KFs. MiR-7-5p was targeted by circ_0057452, and its inhibition overturned the effects of circ_0057452 knockdown. In addition, GAB1 was a target of miR-7-5p, and GAB1 upregulation abolished the role of miR-7-5p overexpression and circ_0057452 knockdown in KFs. Circ_0057452 regulated the expression of GAB1 by adsorbing miR-7-5p in KFs. Circ_0057452 knockdown suppressed keloid development by regulating miR-7-5p/GAB1 axis, which might provide a promising therapeutic target for keloid.
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Project description:Introduction:LncRNA FEZF1-AS1 has been reported to be an oncogene in many types of cancer, while its role in glioblastoma (GBM) is unknown. This study aimed to investigate the potential involvement of FEZF1-AS1 in GBM. Methods:FEZF1-AS1 expression in paired GBM and non-tumor tissues from GBM patients was determined by RT-qPCR. A 2-year follow-up was performed to analyze the prognostic value of FEZF1-AS1 for GBM. Cell transfections were performed to analyze the interactions between FEZF1-AS1, miR-34a and Notch-1. Transwell assay was performed to analyze the role of FEZF1-AS1, miR-34a and Notch-1 in regulating GBM cell invasion and migration. Results:In this study, analysis of TCGA dataset revealed the upregulation of FEZF1-AS1 in GBM, and the overexpression of FEZF1-AS1 in GBM was further confirmed using GBM tissues from GBM patients included in this study. High levels of FEZF1-AS1 were correlated with poor survival. FEZF1-AS1 was predicted to form base pairing with miR-34a. However, overexpression of FEZF1-AS1 and miR-34a failed to affect the expression of each other. However, upregulation of Notch-1, a target of miR-34a, was observed after FEZF1-AS1 in GBM cells. Moreover, increased invasion and migration rates of GBM cells were observed after FEZF1-AS1 and Notch-1 overexpression. MiR-34a played an opposite role and reduced the effects of FEZF1-AS1 and Notch-1 overexpression. Conclusion:FEZF1-AS1 may sponge miR-34a to upregulate Notch-1 in GBM, thereby promoting cancer cell invasion and migration.
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Project description:Long noncoding RNAs (lncRNAs) are important regulators of the biological functions and underlying molecular mechanisms of colorectal cancer (CRC). However, the role of the lncRNA ZEB1-AS1 in CRC is not thoroughly understood. In this study, we found that ZEB1-AS1 was markedly upregulated in CRC. ZEB1-AS1 knockdown significantly suppressed CRC cell proliferation and induced apoptosis, whereas enhanced expression of ZEB1-AS1 had the opposite effect. Bioinformatics analysis identified miR-181a-5p as a candidate target of ZEB1-AS1. Moreover, we found an inverse correlation between ZEB1-AS1 and miR-181a-5p expression in CRC tissue. Inhibition of miR-181a-5p significantly upregulated ZEB1-AS1, whereas overexpression of miR-181a-5p had the opposite effect, suggesting that ZEB1-AS1 is negatively regulated by miR-181a-5p. Using luciferase reporter and RIP assays, we found that miR-181a-5p directly targets ZEB1-AS1. Importantly, ZEB1-AS1 may act as an endogenous 'sponge' to regulate miRNA targets by competing for miR-181a-5p binding. In summary, our findings provide the evidence supporting the role of ZEB1-AS1 as an oncogene in CRC. Our study also demonstrates that miR-181a-5p targets not only protein-coding genes but also the lncRNA ZEB1-AS1.
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Project description:Long noncoding RNAs (lncRNAs) have a certain link to genomic stability (GS). However, the regulatory relationship of lncRNAs and GS has not been thoroughly investigated in hepatocellular carcinoma (HCC). In the present study, samples were retrieved from The Cancer Genome Atlas with somatic mutations and lncRNA expression data. Cox regression analysis was used to identify independent prognostic factors. The RNA levels were determined by reverse transcription‑quantitative PCR and protein levels were detected by western blot analysis. Cell Counting Kit‑8 and colony‑formation assays were used to assess cell viability. Cell migration was measured by wound‑healing and Transwell assays. Cell apoptosis and cell‑cycle progression were evaluated by flow cytometry. GS was detected by alkaline comet and chromosomal aberration assays. A xenograft model and lung metastasis model were used to assess the role of zinc finger protein, FOG family member 2 antisense 1 (ZFPM2‑AS1) in tumor growth in vivo. The molecular mechanisms underlying the biological functions of ZFPM2‑AS1 were investigated through bioinformatics prediction, RNA pull‑down and luciferase reporter assays. A total of 85 genomic instability‑related lncRNAs were identified and a prognostic model was developed. The prognostic model exhibited good predictive power (area under the receiver operating characteristic curve, 0.786). ZFPM2‑AS1 was significantly upregulated in tumor tissues (P<0.001) and it promoted DNA damage repair (P<0.01) and tumor progression in vitro and in vivo. Luciferase reporter assays demonstrated that miR‑3065‑5p was able to bind directly with ZFPM2‑AS1 and X‑ray repair cross complementing 4 (XRCC4). ZFPM2‑AS1 upregulated XRCC4 expression by acting as a sponge (P<0.001). In the present study, a prognostic model for HCC was developed and validated, and one lncRNA of its components was experimentally investigated. ZFPM2‑AS1 regulates XRCC4 by sponging miR‑3065‑5p to promote GS and HCC progression.
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Project description:Gastric cancer (GC) is among the most lethal tumors worldwide. Long noncoding RNAs (lncRNAs) are reported to be critical during the occurrence and progression of malignancies. The HOXC cluster antisense RNA 1 (HOXC-AS1) has been suggested to participate in the genesis and development of GC. Therefore, we examined GC cells and tissues for the expression of HOXC-AS1 and correlated the expression levels with the disease specific survival of the patients, finding that HOXC-AS1 was overexpressed and probably had a tendency of leading to a poor prognosis. The Cell Counting Kit-8 assay and colony formation assay were then performed under knockdown of HOXC-AS1, revealing that cell proliferation of GC was distinctly decreased. Afterwards, miR-99a-3p was predicted to bind with HOXC-AS1 by DIANA tools. We carried out dual-luciferase reporter gene assays to identify the interaction between them. After knockdown of HOXC-AS1, miR-99a-3p was clearly overexpressed in GC cells. In addition, matrix metalloproteinase 8 (MMP8) was shown to be combined with miR-99a-3p using TargetScan. Similar experiments, along with western blot, were conducted to validate the correlation between miR-99a-3p and MMP8. Finally, rescue experiments for CCK-8 were completed, disclosing that HOXC-AS1 promoted cell progression of GC through sponging miR-99a-3p followed by subsequent upregulation of MMP8.
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Project description:IntroductionLncRNAs have been reported to play critical roles in liver cancer, while its role in other cancers remains unclear. The aim of this study was to investigate the role of DCST1-AS1 in cervical squamous cell carcinoma (CSCC).MethodsExpression of DCST1-AS1 in CSCC tissues and non-tumor tissues from 68 CSCC patients was determined by RT-qPCR. A 5-year follow-up study was carried out to explore the prognostic value of DCST1-AS1 for CSCC. Overexpression of DCST1-AS1 and miR-107 was achieved in CSCC tissues to explore the interaction between them. The roles of DCST1-AS1, miR-107 and CDK6 in regulating the proliferation and viability of CSCC cells were assessed by cell proliferation and viability assays, respectively.ResultsWe found that DCST1-AS1 was upregulated in CSCC and predicted poor survival. RNA interaction prediction showed potential interaction between DCST1-AS1 and miR-107. However, overexpression experiments revealed no significant interaction between them. Moreover, overexpression of DCST1-AS1 led to upregulate CDK6 and increase cell proliferation rate, while overexpression of miR-107 played an opposite role and attenuate the effects of overexpression of DCST1-AS1.ConclusionDCST1-AS1 may sponge miR-107 to upregulate CDK6 in CSCC.
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Project description:BackgroundHepatocellular carcinoma (HCC) is the most common malignant liver tumor with poor clinical outcomes. Increasing amount of long non-coding RNAs (lncRNAs) have been revealed to be implicated in the carcinogenesis and progression of HCC. However, the expressions, clinical significances, and roles of most lncRNAs in HCC are still unknown.MethodsThe expression of lncRNA MCM3AP antisense RNA 1 (MCM3AP-AS1) in HCC tissues and cell lines was detected by qRT-PCR and fluorescence in situ hybridization. Immunoblotting, CCK-8, EdU, colony formation and flow cytometry were performed to investigate the role of MCM3AP-AS1 in HCC cell proliferation, cell cycle and apoptosis in vitro. A subcutaneous tumor mouse model was constructed to analyze in vivo growth of HCC cells after MCM3AP-AS1 knockdown. The interactions among MCM3AP-AS1, miR-194-5p and FOXA1 were measured by RNA pull-down, RNA immunoprecipitation and luciferase reporter assay.ResultsWe revealed a novel oncogenic lncRNA MCM3AP-AS1, which is overexpressed in HCC and positively correlated with large tumor size, high tumor grade, advanced tumor stage and poor prognosis of HCC patients. MCM3AP-AS1 knockdown suppressed HCC cell proliferation, colony formation and cell cycle progression, and induced apoptosis in vitro, and depletion of MCM3AP-AS1 inhibited tumor growth of HCC in vivo. Mechanistically, MCM3AP-AS1 directly bound to miR-194-5p and acted as competing endogenous RNA (ceRNA), and subsequently facilitated miR-194-5p's target gene forkhead box A1 (FOXA1) expression in HCC cells. Interestingly, FOXA1 restoration rescued MCM3AP-AS1 knockdown induced proliferation inhibition, G1 arrest and apoptosis of HCC cells.ConclusionsOur results recognized MCM3AP-AS1 as a novel oncogenic lncRNA, which indicated poor clinical outcomes in patients with HCC. MCM3AP-AS1 exerted an oncogenic role in HCC via targeting miR-194-5p and subsequently promoted FOXA1 expression. Our findings suggested that MCM3AP-AS1 could be a potential prognostic biomarker and therapeutic target for HCC.
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Project description:Hepatocellular carcinoma (HCC) belongs to the most frequent cancer with a high death rate worldwide. Thousands of long non-coding RNAs (lncRNAs) have been confirmed to influence the development of human cancers, including HCC. Nevertheless, the biological role of PRR34 antisense RNA 1 (PRR34-AS1) in HCC remains obscure. Here, we observed via quantitative real-time reverse transcriptase polymerase chain reaction (quantitative real-time RT-PCR) that PRR34-AS1 was highly expressed in HCC cells. Functional assays revealed that PRR34-AS1 promoted HCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process in vitro and facilitated tumor growth in vivo. In addition, western blot analysis and TOP Flash/FOP Flash reporter assays verified that PRR34-AS1 stimulated Wnt/β-catenin pathway in HCC cells. Furthermore, RNA immunoprecipitation (RIP), RNA pull-down, and luciferase reporter assays uncovered that PRR34-AS1 sequestered microRNA-296-5p (miR-296-5p) to positively modulate E2F transcription factor 2 (E2F2) and SRY-box transcription factor 12 (SOX12) in HCC cells. Importantly, chromatin immunoprecipitation (ChIP) and luciferase reporter assays uncovered that E2F2 transcriptionally activated PRR34-AS1 in turn. Further, rescue experiments reflected that PRR34-AS1 affected HCC progression through targeting miR-296-5p/E2F2/SOX12/Wnt/β-catenin axis. Our findings found that PRR34-AS1 elicited oncogenic functions in HCC, which indicated that PRR34-AS1 might be a novel therapeutic target for HCC.
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Project description:Glioblastoma, one of the most fatal brain tumors, is associated with a dismal prognosis and an extremely short overall survival. We previously reported that the overexpressed transient receptor potential channel TRPM7 is an essential glioblastoma regulator. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in glioma's initiation and progression. However, the function of lncRNA, HOX transcript antisense intergenic RNA (HOTAIR) mediated by TRPM7 in glioma remains unclear. In this study, HOTAIR expression was found to be positively regulated by TRPM7, significantly upregulated in glioma tissues, and is a poor prognosis factor for glioma patients. Moreover, reduced HOTAIR expression impeded the proliferation and invasion of glioma cells. Mechanistically, HOTAIR directly interacted with miR-301a-3p, and downregulation of miR-301a-3p efficiently reversed FOSL1 suppression induced by siRNA HOTAIR, which implied that HOTAIR positively regulated FOSL1 level through sponging miR-301a-3p and played an oncogenic role in glioma progression. In contrast to HOTAIR's role, miR-301a-3p alone served as a tumor suppressor to decrease glioma cell viability and migration/invasion. In agreement with HOTAIR's role, FOSL1 functioned as a tumorigenic gene in glioma pathogenesis, which was highly expressed in glioma tissues, and was shown to be an unfavorable prognostic factor for glioma patients. Mechanically, FOSL1 inhibition by siRNA FOSL1 efficiently rescued the oncogenic-like phenotypes caused by the miR-301a-3p inhibitor in glioma pathogenesis. SIGNIFICANCE: Our study elucidated the role of TRPM7-mediated HOTAIR as a miRNA sponge to target downstream FOSL1 oncogene and therefore consequently contribute to gliomagenesis, which shed new light on TRPM7/lncRNA-directed diagnostic and therapeutic approach in glioma.
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