Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1

Chen, Zhenyao; Chen, Qinnan; Cheng, Zhixiang; Gu, Jianqin; Feng, Wenyan; Lei, Tianyao; Huang, Jiana; Pu, Jiaze; Chen, Xin; Wang, Zhaoxia

doi:10.1038/s41419-020-03047-y

Cited by 80 publications

(55 citation statements)

References 39 publications

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“…Multiple cancer-related lncRNAs have been identified, such as MALAT1, HOTAIR, lncRNA-ATB, FAL1, EPIC1, LINK-A, and PXN-AS1 ( Gutschner et al, 2013 ; Hu et al, 2014 ; Yuan et al, 2014 ; Lin et al, 2016 ; Yuan et al, 2017 ; Wang et al, 2018 ; Li H. et al, 2020 ). In lung cancer, lncRNAs PIK3CD-AS2, HCP5, SNHG15, SNHG11, CASC9, and ALAL-1 have oncogenic roles ( Athie et al, 2020 ; Cheng et al, 2020 ; Chen Z. et al, 2020 ; Huang et al, 2020 ; Li C. et al, 2020 ; Zheng et al, 2020 ). In contrast, lncRNAs NORAD, BRCAT54, CASC7, and HSPC324 have tumor-suppressive roles ( Tan et al, 2019 ; Chen L. et al, 2020 ; Jafarzadeh et al, 2020 ; Yang et al, 2020 ).…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…Currently, it was urgent for us to improve the prognosis of NSCLC patients by finding novel and improved therapies. More and more evidences have showed that a large number of lncRNAs played extremely pivotal biological roles in the progression of NSCLC (20). For example, LncRNA KTN1-AS1, CASC9, ABHD11-AS1, LINC00467 could participate in the progress of NSCLC (20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

The Regulatory Network and Potential Role of LINC00973-miRNA-mRNA ceRNA in the Progression of Non-Small-Cell Lung Cancer

Guo

Luo

et al. 2021

Front. Immunol.

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BackgroundThe occurrence and development of cancer could be promoted by abnormally competing endogenous RNAs (ceRNA) network. This article aims to determine the prognostic biomarker of ceRNA for non-small-cell lung cancer (NSCLC) prognosis.MethodsThe expression and clinical significance of LINC00973 in NSCLC tissues were analyzed via the The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), lnCAR, and clinical samples in Taihe Hospital. The biological functions and signaling pathways involved in target genes of ceRNA network were analyzed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis, univariate and multivariate Cox regression analysis were used for prognostic-related mRNA.ResultsExpression of LINC00973 was increased in NSCLC tissues. High expression of LINC00973 was associated with poor prognosis of NSCLC patients. There were 15 miRNA and 238 differential mRNA in the INC00973-miRNA-mRNA ceRNA network, involving cell migration, endothelial cell proliferation, tumor growth factor (TGF)-β, cellular senescence, phosphatidylinositol 3-hydroxy kinase (PI3K)-Akt, Hippo, Rap1, mitogen-activated protein kinase (MAPK), cell cycle signaling pathway, etc. The expression levels of RTKN2, NFIX, PTX3, BMP2 and LOXL2 were independent risk factors for the poor prognosis of NSCLC patients.ConclusionsLINC00973-miRNA-mRNA ceRNA network might be the basis for determining pivotal post-translational regulatory mechanisms in the progression of NSCLC. BMP2, LOXL2, NFIX, PTX3 and RTKN2 might be valuable prognostic markers and potential therapeutic targets.

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“…Top‐ranked genes in this signature are known downstream targets of EZH2 and play a proven role in tumorigenesis (Supplementary Table S8). For example, EZH2 binds to the DUSP1 promoter inducing H3K27 trimethylation, which subsequently suppresses DUSP1 expression 48 . EZH2 also directly regulates the key tumour suppressor, miRNA101, in a negative feedback loop 49 and decreasing levels of miRNA101 are associated with multiple tumours, including colon, liver, lung, ovarian and prostate 50 .…”

Section: Discussionmentioning

confidence: 99%

A rare variant in EZH2 is associated with prostate cancer risk

Raspin

FitzGerald

Marthick

et al. 2021

Intl Journal of Cancer

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Prostate cancer (PrCa) is highly heritable, and although rare variants contribute significantly to PrCa risk, few have been identified to date. Herein, whole-genome sequencing was performed in a large PrCa family featuring multiple affected relatives spanning several generations. A rare, predicted splice site EZH2 variant, rs78589034 (G > A), was identified as segregating with disease in all but two individuals in the family, one of whom was affected with lymphoma and bowel cancer and a female relative. This variant was significantly associated with disease risk in combined familial and sporadic PrCa datasets (n = 1551; odds ratio [OR] = 3.55, P = 1.20 × 10 −5 ).Transcriptome analysis was performed on prostate tumour needle biopsies available for two rare variant carriers and two wild-type cases. Although no allele-dependent differences were detected in EZH2 transcripts, a distinct differential gene expression signature was observed when comparing prostate tissue from the rare variant carriers with the wild-type samples. The gene expression signature comprised known downstream targets of EZH2 and included the top-ranked genes, DUSP1, FOS, JUNB and EGR1, which were subsequently validated by qPCR. These data provide evidence that rs78589034 is associated with increased PrCa risk in Tasmanian men and further, that this variant may be associated with perturbed EZH2 function in prostate tissue. Disrupted EZH2 function is a driver of tumourigenesis in several cancers, including prostate, and is of significant interest as a therapeutic target.

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Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1

Cited by 80 publications

References 39 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

The Regulatory Network and Potential Role of LINC00973-miRNA-mRNA ceRNA in the Progression of Non-Small-Cell Lung Cancer

A rare variant in EZH2 is associated with prostate cancer risk

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