LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC

Yi, Tie-Zhong; Song, Yicun; Zuo, Lingling; Wang, Siyun; Miao, Jintian

doi:10.3389/fonc.2021.646217

Cited by 17 publications

(12 citation statements)

References 33 publications

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“…[ 42 ] indicated that knockdown of LINC00470 expression inhibited cell proliferation and cell cycle progression, while overexpression of LINC00470 showed the opposite effects in hepatocellular carcinoma. In addition, LINC00470 promoted invasiveness, migration, and angiogenesis of endometrial cancer cells [ 43 ]. Knockdown of LINC00470 could significantly inhibit the melanoma cell proliferation and migration, and suppress the growth of tumor in vivo [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of an eight-lncRNA signature that predicts prognosis in patients with esophageal squamous cell carcinoma

et al. 2022

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Background Esophageal squamous cell carcinoma (ESCC) is correlated with worse clinical prognosis and lacks available targeted therapy. Thus, identification of reliable biomarkers is required for the diagnosis and treatment of ESCC. Methods We downloaded the GSE53625 dataset as a training dataset to screen differentially expressed RNAs (DERs) with the criterion of false discovery rate (FDR) < 0.05 and |log2fold change (FC)| > 1. A support vector machine classifier was used to find the optimal feature gene set that could conclusively distinguish different samples. An eight-lncRNA signature was identified by random survival forest algorithm and multivariate Cox regression analysis. The RNA sequencing data from The Cancer Genome Atlas (TCGA) database were used for external validation. The predictive value of the signature was assessed using Kaplan–Meier test, time-dependent receiver operating characteristic (ROC) curves, and dynamic area under the curve (AUC). Furthermore, a nomogram to predict patients’ 3-year and 5-year prognosis was constructed. CCK-8 assay, flow cytometry, and transwell assay were conducted in ESCC cells. Results A total of 1136 DERs, including 689 downregulated mRNAs, 318 upregulated mRNAs, 74 downregulated lncRNAs and 55 upregulated lncRNAs, were obtained in the GES53625 dataset. From the training dataset, we identified an eight-lncRNA signature, (ADAMTS9-AS1, DLX6-AS1, LINC00470, LINC00520, LINC01497, LINC01749, MAMDC2-AS1, and SSTR5-AS1). A nomogram based on the eight-lncRNA signature, age, and pathologic stage was developed and showed good accuracy for predicting 3-year and 5-year survival probability of patients with ESCC. Functionally, knockdown of LINC00470 significantly suppressed cell proliferation, G1/S transition, and migration in two ESCC cell lines (EC9706 and TE-9). Moreover, knockdown of LINC00470 downregulated the protein levels of PCNA, CDK4, and N-cadherin, while upregulating E-cadherin protein level in EC9706 and TE-9 cells. Conclusion Our eight-lncRNA signature and nomogram can provide theoretical guidance for further research on the molecular mechanism of ESCC and the screening of molecular markers.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of an eight-lncRNA signature that predicts prognosis in patients with esophageal squamous cell carcinoma

et al. 2022

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“…We followed the specific steps as described in a previous publication [30]. Whole genomic DNA was extracted, and unmethylated cytosines in which were converted to uracil.…”

Section: Methylation-specific Pcr Detectionmentioning

confidence: 99%

“…For instance, LINC00470 facilitated phenotypes of gastric cancer cells via the promotion of PTEN mRNA degradation [28]. LINC00470 stimulated methylation of PTEN to facilitate the progression of endometrial cancer by recruiting DNMT3a via MYC [30]. LINC00470 directly interacted with FUS and repressed autophagy as an AKT activator to facilitate glioma cell phenotypes.…”

Section: Introductionmentioning

confidence: 99%

LINC00470 represses cell autophagy and cisplatin sensitivity of glioma via suppressing PTEN expression

Chen¹,

Wang²,

Lin³

et al. 2023

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Introduction: Glioma is one of primary brain tumours which has the worst clinical prognoses of patients. As an alternative chemotherapeutic drug for malignant glioma, the therapeutic effect of cisplatin (CDDP) is devastatingly affected due to resistance in patients. In this study, we investigated the effect of LINC00470/PTEN on the CDDP sensitivity of glioma cells. Material and methods: Differentially expressed lncRNAs and the downstream regulators in glioma tissue were obtained via bioinformatics analysis. LINC00470 and PTEN mRNA expression levels were detected using qRT-PCR. IC50 values of glioma cells were examined using Cell Counting . Cell apoptosis was revealed by flow cytometry. The expression level of autophagy-related protein was detected by western blot. Intracellular autophagosome formation was detected by immunofluorescence staining, and the methylation level of PTEN promoter was detected via methylation-specific PCR (MSP).Results: Through the above steps, we found that LINC00470 was highly expressed in glioma cells, and the survival rate of patients was reduced in the presence of high expression of LINC00470. Silenced LINC00470 promoted LC3 II expression and autophagosome formation, and facilitated cell apoptosis to inhibit resistance to CDDP. While silenced PTEN could successfully reverse the previous effects on glioma cells. Conclusions: Based on the above, LINC00470 repressed cell autophagy by constraining PTEN, thereby enhancing CDDP resistance of glioma cells.

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“…Recently, regulating PTEN promotor methylation has been reported to play an important role in the progression of EC. The research of Yi et al, demonstrated that Linc00470 recruited DNMT3a through MYC to promote PTEN methylation and promote angiogenesis and metastasis of EC cells in vivo [ 112 ]. Chen et al, demonstrated that Piwil1 repressed PTEN expression through DNMT1-mediated PTEN hypermethylation in type I ECs [ 113 ].…”

Section: Tumor Suppressor Genesmentioning

confidence: 99%

Research Progress of DNA Methylation in Endometrial Cancer

Ding

Chen

et al. 2022

Biomolecules

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Endometrial cancer (EC)) is one of the most common malignant tumors of the female genital system, with an increasing incidence and mortality, worldwide. Although the therapeutic strategy of EC is still complicated and challenging, further understanding of carcinogenesis from a gene perspective would allow an effort to improve therapeutic precision in this complex malignancy. DNA methylation is the most widely studied epigenetic alteration in human tumors. Aberrant DNA methylation events, resulting in altered gene expression, are features of many tumor types. In this review, we provide an update on evidence about the roles of aberrant DNA methylation within some classical tumor suppressor genes and oncogenes in endometrial carcinogenesis, and report on recent advances in the understanding of the contribution of aberrant DNA methylation to EC, as well as opportunities and challenges of DNA methylation in EC management and prevention.

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LINC00470 Stimulates Methylation of PTEN to Facilitate the Progression of Endometrial Cancer by Recruiting DNMT3a Through MYC

Cited by 17 publications

References 33 publications

Identification and validation of an eight-lncRNA signature that predicts prognosis in patients with esophageal squamous cell carcinoma

Identification and validation of an eight-lncRNA signature that predicts prognosis in patients with esophageal squamous cell carcinoma

LINC00470 represses cell autophagy and cisplatin sensitivity of glioma via suppressing PTEN expression

Research Progress of DNA Methylation in Endometrial Cancer

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