lncRNA DLGAP1-AS2 Knockdown Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Regulating miR-154-5p Methylation

Chen, Kai; Zhang, Zhuqing; Yu, Aijun; Li, Jian; Liu, Jinlong; Zhang, Xuejun

doi:10.1155/2020/6575724

Cited by 14 publications

(13 citation statements)

References 17 publications

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“…By conducting combined functional assays such as cell proliferation assay, clonogenic assay, apoptotic assay, Transwell assay, and xenograft model, we were able to demonstrate that DLGAP1-AS2 drove the malignancy and progression of GC. Generally considered as an oncogenic factor, DLGAP1-AS2 has recently been reported to modulate the tumorigenesis and progression of several tumors, such as HCC [ 24 ], CCA [ 25 ], and Glioma [ 26 ]. The reported mechanisms of DLGAP1-AS2 range from ceRNA to epigenetic modification, suggesting versatile roles for DLGAP1-AS2 in the regulation of cancer biology.…”

Section: Discussionmentioning

confidence: 99%

“…Located at chromosome 18p11.31, DLGAP1-AS2 is a lncRNA that was first reported in patients with Wilms’ tumor and may serve as a prognostic marker [ 23 ]. And researchers also found that DLGAP1-AS2 is significantly upregulated in several cancers such as glioma, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CCA) [ 24 – 26 ]. The reported mechanisms of DLGAP1-AS2 range from competing endogenous RNA (ceRNA) to epigenetic modification, suggesting versatile roles for DLGAP1-AS2 in the regulation of cancer biology.…”

Section: Introductionmentioning

confidence: 99%

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Long noncoding RNA DLGAP1-AS2 facilitates Wnt1 transcription through physically interacting with Six3 and drives the malignancy of gastric cancer

Xü

Xie

et al. 2021

Cell Death Discov.

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The long noncoding RNA (lncRNA) DLGAP1-AS2 has recently been characterized as an oncogenic lncRNA in several cancers. However, its biological roles and clinical significance in gastric cancer (GC) remains barely understood. In this study, we performed a systematic analysis of DLGAP1-AS2 expression with data from the TCGA and GEO database as well as our clinic GC samples. In agreement with previous studies, our findings demonstrated that DLGAP1-AS2 was significantly up-regulated in GC and its high expression was associated with poor prognosis, suggesting that DLGAP1-AS2 might be a putative oncogenic lncRNA of GC. Loss of DLGAP1-AS2 restricted cell proliferation, migration, and invasion in GC cell lines. Mechanically, Wnt1 was identified as the downstream target of DLGAP1-AS2 by using bioinformatics analysis coupled with qPCR and Western blot assays. Furthermore, DLGAP1-AS2 was found to directly interact with the transcriptional repressor Six3, and this interaction hampered Six3 binding to the promoter regions of the Wnt1 gene, thereby leading to transcriptional activation of Wnt1. Consequently, GC cells lacking DLGAP1-AS2 showed a decreased Wnt1 expression and weakened Wnt/β-catenin signaling. Further, Six3 silencing could reverse the above effects, highlighting a pivotal role of Six3 in the DLGAP1-AS2-mediated activation of Wnt/β-catenin signaling. Either genetic (Wnt1 knockdown) or pharmacological (LF3) inhibition of Wnt/β-catenin signaling could effectively abolish the activation of Wnt/β-catenin signaling by Six3 depletion, thereby preventing GC cell malignant transformation. Taken together, our results suggest that DLGAP1-AS2 functions as an oncogenic factor by directly interacting with Six3 to relieve its suppression on Wnt1 expression, thereby driving the malignancy of GC. DLGAP1-AS2/Six3/Wnt1/β-catenin signaling axis might serve as a promising diagnostic and therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA DLGAP1-AS2 facilitates Wnt1 transcription through physically interacting with Six3 and drives the malignancy of gastric cancer

Xü

Xie

et al. 2021

Cell Death Discov.

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“…Here, we systematically evaluated the ferroptosis-related lncRNAs in WT patients and generated a ferroptosis- previously shown to target YAPP1 and promote glioma tumorigenesis (31). In addition, it was also shown to promote hepatocellular carcinoma and cholangiocarcinoma progression via regulation of miR-154 and miR-505, respectively (32,33). However, other ferroptosis-related lncRNAs have not been studied in relation to tumors, and, therefore, requires additional investigation.…”

Section: Discussionmentioning

confidence: 99%

Identification of a ferroptosis-related lncRNA signature with prognosis for Wilms tumor

Liu¹,

Zhang²,

Zhang³

et al. 2021

Transl Pediatr

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Background: Wilms tumor (WT) is a widespread urologic tumor in children. Ferroptosis, on the other hand, is a novel form of cell death associated with tumor development. In this study, we aim to explore the predictability of ferroptosis-related biomarkers in estimating prognosis in WT patients.Methods: To determine a link between ferroptosis-related gene expression and WT prognosis, we first collected RNA sequencing data and clinical information, involving 124 WT and 6 healthy tissue samples, from the TARGET database. Next, we screened the collected information for ferroptosis-related long noncoding RNA using Cox regression analysis, and constructed a signature model, as well as a nomogram, related to prognosis. Finally, we explored a potential link between ferroptosis-related lncRNA and tumor immunity and screened for possible immune checkpoints.Results: We constructed a WT prognosis prediction signature containing 12 ferroptosis-related lncRNAs.The area under the curves values, from the ROC curves, predicting overall survival rates at the 1, 3-, and 5-year timepoints were 0.775, 0.867, and 0.891 respectively. Moreover, we generated a nomogram, using clinical features and risk scores, carrying a C-index value of 0.836, which suggested a high predictive value.We also demonstrated significant differences in tumor immunity between low-and high-risk WT patients, particularly in the presence of B cells, NK cells, Th1 cells, Treg cells, inflammation promoting, and type I and II IFN responses. In addition, we showed that immune checkpoints like SIRPA, ICOSLG, LAG3, PVRIG, NECTIN1, and SIRPB2 can serve as potential therapeutic targets for WT.Conclusions: Based on our analyses, we generated a ferroptosis-related lncRNA signature that can both estimate prognosis of WT patients and may provide basis for future WT therapy.

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“…Recent research had shown that dysregulated lncRNA plays an important role in many diseases, such as tumor, cardiovascular diseases, and metabolic disorders [17,18]. Dysregulated lncRNA is closely associated with tumor growth and metastasis observed in cancers such as breast, lung, liver, and colorectal cancers [19][20][21]. Some studies have suggested that lncRNAs may potentially serve as biomarkers and targets in diagnosing and treating tumors.…”

Section: Introductionmentioning

confidence: 99%

Identification of N6-methylandenosine related LncRNAs biomarkers associated with the overall survival of osteosarcoma

Zhang

Wang

et al. 2021

BMC Cancer

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Purpose Osteosarcoma (OS) is a differentiation disease caused by the genetic and epigenetic differentiation of mesenchymal stem cells into osteoblasts. OS is a common, highly malignant tumor in children and adolescents. Fifteen to 20 % of the patients find distant metastases at their first visit. The purpose of our study was to identify biomarkers for tracking the prognosis and treatment of OS to improve the survival rate of patients. Materials and methods In this study, which was based on Therapeutically Applicable Research to Generate Effective Treatments (TARGET), we searched for m6A related lncRNAs in OS. We constructed a network between lncRNA and m6A, and built an OS prognostic risk model. Results We identified 14,581 lncRNAs by using the dataset from TARGET. We obtained 111 m6A-related lncRNAs through a Pearson correlation analysis. A network was built between lncRNA and m6A genes. Eight m6A-related lncRNAs associated with survival were identified through a univariate Cox analysis. A selection operator (LASSO) Cox regression was used to construct a prognostic risk model with six genes (RP11-286E11.1, LINC01426, AC010127.3, DLGAP1-AS2, RP4-657D16.3, AC002398.11) obtained through least absolute shrinkage. We also discovered upregulated levels of DLGAP1-AS2 and m6A methylation in osteosarcoma tissues/cells compared with normal tissues/osteoblasts cells. Conclusion We constructed a risk score prognosis model of m6A-related lncRNAs (RP11-286E11.1, LINC01426, AC010127.3, DLGAP1-AS2, RP4-657D16.3, AC002398.11) using the dataset downloaded from TRAGET. We verified the value of the model by dividing all samples into test groups and training groups. However, the role of m6A-related lncRNAs in osteosarcoma needs to be further researched by cell and in vivo studies.

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lncRNA DLGAP1-AS2 Knockdown Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Regulating miR-154-5p Methylation

Cited by 14 publications

References 17 publications

Long noncoding RNA DLGAP1-AS2 facilitates Wnt1 transcription through physically interacting with Six3 and drives the malignancy of gastric cancer

Long noncoding RNA DLGAP1-AS2 facilitates Wnt1 transcription through physically interacting with Six3 and drives the malignancy of gastric cancer

Identification of a ferroptosis-related lncRNA signature with prognosis for Wilms tumor

Identification of N6-methylandenosine related LncRNAs biomarkers associated with the overall survival of osteosarcoma

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