Silencing of LncRNA C1RL-AS1 Suppresses the Malignant Phenotype in Gastric Cancer Cells via the AKT/β-Catenin/c-Myc Pathway

Wu, Zhenhua; Gong, Yaoqin; Zhao, Liang; Zhang, Jieyun; Gong, Zhe; Guo, Weijian

doi:10.3389/fonc.2020.01508

Cited by 11 publications

(8 citation statements)

References 27 publications

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“…These results demonstrated that ITGB1-DT activated Wnt/β-catenin pathway in LUAD. MYC is a well-known Wnt/β-catenin downstream target and exhibits oncogenic roles in various cancers ( Zhen-Hua et al, 2020 ). Thus, we further detected the effects of ITGB1-DT on MYC expression.…”

Section: Resultsmentioning

confidence: 99%

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

Chang

Xiao

et al. 2021

Front. Cell Dev. Biol.

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Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.

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Section: Resultsmentioning

confidence: 99%

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

Chang

Xiao

et al. 2021

Front. Cell Dev. Biol.

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“…In addition, prostate cancer-associated transcript 6 (PCAT6) could promote the oncogenesis and angiogenesis of triple-negative breast cancer by regulating VEGFR2 ( 35 ). AKT/β-catenin/c-Myc pathway was activated by C1RL-AS1 to promote the cancerous behavior in stomach adenocarcinoma cells ( 36 ). Moreover, by affecting the miR-194-5p/FOXA1 axis, MCM3AP-AS1 has been shown to increase hepatocellular cancer growth ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

A novel m7G-related lncRNA risk model for predicting prognosis and evaluating the tumor immune microenvironment in colon carcinoma

et al. 2022

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N7-Methylguanosine (m7G) modifications are a common type of posttranscriptional RNA modifications. Its function in the tumor microenvironment (TME) has garnered widespread focus in the past few years. Long non-coding RNAs (lncRNAs) played an essential part in tumor development and are closely associated with the tumor immune microenvironment. In this study, we employed a comprehensive bioinformatics approach to develop an m7G-associated lncRNA prognostic model based on the colon adenocarcinoma (COAD) database from The Cancer Genome Atlas (TCGA) database. Pearson’s correlation analysis was performed to identify m7G-related lncRNAs. Differential gene expression analysis was used to screen lncRNAs. Then, we gained 88 differentially expressed m7G-related lncRNAs. Univariate Cox analysis and Lasso regression analysis were performed to build an eight-m7G-related-lncRNA (ELFN1-AS1, GABPB1-AS1, SNHG7, GS1-124K5.4, ZEB1-AS1, PCAT6, C1RL-AS1, MCM3AP-AS1) risk model. Consensus clustering analysis was applied to identify the m7G-related lncRNA subtypes. We also verified the risk prediction effect of a gene signature in the GSE17536 test set (177 patients). A nomogram was constructed to predict overall survival rates. Furthermore, we analyzed differentially expressed genes (DEGs) between high-risk and low-risk groups. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted with the analyzed DEGs. At last, single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, MCP-COUNTER, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithms were utilized to discover the relationship between the risk model and the TME. Consequently, the m7G-related lncRNA risk model for COAD patients could be a viable prognostic tool and treatment target.

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“…miR-16-5p was reported to be sponged by SNHG16, which served as a ceRNA, and so induce the derepression of its target gene SMAD5 and result in potentiation of the TGF-β1/SMAD5 pathway to upregulate the expression of CD73 in Vδ1 T cells [27]. C1RL-AS1 probably promoted the malignant phenotype of gastric cancer via the AKT/β-catenin pathway by downregulating c-Myc [28].…”

Section: Discussionmentioning

confidence: 99%

KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma

Cui

Shen

et al. 2022

Cancer Cell Int

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Background Studies over the past decade have shown that competitive endogenous RNA (ceRNA) plays an essential role in the tumorigenesis and progression of clear cell renal cell carcinoma (ccRCC). Meanwhile, immune checkpoint blocker is gradually moving towards the first-line treatment of ccRCC. Hence, it’s urgent to develop a new prediction model for the efficiency of immunotherapy. At present, there is no study to reveal the effect of ceRNA network on the efficiency of immunotherapy for ccRCC. Methods To systematically analyze the effect of ceRNA hub genes in ccRCCon immune response, we constructed prognosis models based on ceRNAs and immune cells, respectively. We constructed ceRNA network using hypergeometric distribution test and correlation analysis with R script based on The Cancer Genome Atlas (TCGA) database. We then applied the Cibersort algorithm to simulate the infiltration overview of immune cells in kidney renal clear carcinoma (KIRC) samples. Prognosis-related immune cells were screened and a predictive model of these cells was constructed. Prognosis-related immune cells and ceRNA hub genes were performed with co-expression analysis. Finally, qRT-PCR and immunofluorescence assays were performed to validate the results. Results The construction of ceRNA related prognosis model contained 8 hub genes, including RELT, MYO9B, KCNN4, SIX1, OTOGL, MALAT1, hsa-miR-130b-3p, and hsa-miR-21-5p. The area under the receiver operating characteristic curve (AUC) was 0.77 at 5 years. For the construction of immune cells prognosis model, 3 immune cells (T cells regulatory, Macrophages, Mast cells resting) were adopted, and the AUC was 0.65 at 5 years. We then merged the two models by correlation analysis and co-expression analysis. Finally, we found that KCNN4 positively correlates with T cells regulatory (Tregs) and negatively correlates with mast cells resting significantly. Furthermore, higher expression of KCNN4 may lead to a higher potential for immune evasion and lower efficiency for immune checkpoint inhibitors (ICIs). Conclusions Generally, this is the first study to assess the prognostic value of immune related ceRNA hub genes in ccRCC, and KCNN4 was finally demonstrated to be a key regulatory factor with strong correlation with Tregs and mast cells resting.

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Silencing of LncRNA C1RL-AS1 Suppresses the Malignant Phenotype in Gastric Cancer Cells via the AKT/β-Catenin/c-Myc Pathway

Cited by 11 publications

References 27 publications

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

A novel m7G-related lncRNA risk model for predicting prognosis and evaluating the tumor immune microenvironment in colon carcinoma

KCNN4 may weaken anti-tumor immune response via raising Tregs and diminishing resting mast cells in clear cell renal cell carcinoma

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