Dataset Information

Super-Enhancer LncRNA LINC00162 Promotes Progression of Bladder Cancer.

ABSTRACT: Due to the lack of effective early diagnostic measures and treatment methods, bladder cancer has become a malignant tumor that seriously threatens people's lives and health. Here, we reported that LINC00162, a super-enhancer long noncoding RNA, was highly expressed in bladder cancer cells and tissues. And LINC00162 was negatively correlated with neighboring PTTG1IP expression. Knocking down LINC00162 expression can inhibit the proliferative activity of bladder cancer cells and the growth of transplanted tumors in vivo, while knocking down the expression of PTTG1IP could restore the proliferative activity of bladder cancer cells. In addition, both LINC00162 and PTTG1IP were found to be able to bind to THRAP3, a transcription-related protein. And THRAP3 can regulate PTTG1IP expression. Finally, we demonstrated a mechanism that LINC00162 could regulate PTTG1IP expression through binding THRAP3. This study provided a potential target molecule for clinical treatment of bladder cancer.

SUBMITTER: Wang X

PROVIDER: S-EPMC7736918 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Super-Enhancer LncRNA LINC00162 Promotes Progression of Bladder Cancer.

Wang Xin X Zhang Ruirui R Wu Shuilian S Shen Liping L Ke Meixia M Ouyang Yan Y Lin Mengqi M Lyu Yiting Y Sun Binuo B Zheng Zhijian Z Yang Jialei J Yang Jie J Lu Wenmin W Yang Yiping Y Li Danni D Zou Yunfeng Y Huang Haishan H Nan Aruo A

iScience 20201124 12

Due to the lack of effective early diagnostic measures and treatment methods, bladder cancer has become a malignant tumor that seriously threatens people's lives and health. Here, we reported that LINC00162, a super-enhancer long noncoding RNA, was highly expressed in bladder cancer cells and tissues. And LINC00162 was negatively correlated with neighboring PTTG1IP expression. Knocking down LINC00162 expression can inhibit the proliferative activity of bladder cancer cells and the growth of tran ...[more]

PMID: 33344916

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Project description:Simple Summary Based on the latest research, cancer cells prefer glutamine to glucose. Therefore, it is more worthwhile to explore the regulatory mechanism of glutamine metabolism in cancer cells. Super enhancers are critical for the gene transcriptional programs responsible for cell fate by interacting with various transcription factors. The transcription factor HSF1 exerts a multifaced role in tumorigenesis. However, the relevance of HSF1 to super enhancers in tumors remains obscure. Therefore, this study focused on the mechanism underlying super-enhancer activation and its relationship to HSF1 in CRC. Here, we performed a super-enhancer landscape in CRC and we screened out an HSF1-mediated super enhancer, lncRNA-LINC00857, by lncRNA microarray. We discovered that HSF1 could stimulate acetyltransferase P300-mediated super-enhancer activity to facilitate LINC00857 expression, contributing to SLC1A5/ASCT2-mediated glutamine transport. In addition, we validated that targeting the HSF1/LINC00857/ANXA11 axis may provide a valuable therapeutic strategy against CRC. Abstract Super enhancers are critical for the gene transcription responsible for cell fate by interacting with transcription factors. However, the relevance of HSF1 to super enhancers in tumors remains obscure. We profiled H3K27ac enrichment by chromatin immunoprecipitation sequencing. HSF1-mediated lncRNAs were identified by lncRNA microarray. The characteristics of LINC00857 were explored by in vitro and in vivo assays. The mechanism was studied via chromatin immunoprecipitation, RNA immunoprecipitation, and HSF1/ANXA11 knockout mice. We found that super enhancers occupied multiple gene loci in colorectal cancer. We screened out an HSF1-mediated super enhancer, lncRNA-LINC00857, which exerts its characteristics in promoting cell growth via regulating glutamine metabolism. Notably, HSF1 could stimulate the super-enhancer activity of LINC00857 by the enrichment of acetyltransferase P300 to its gene loci, contributing to LINC00857 transcription. In turn, nuclear LINC00857 cooperated with HSF1 to promote ANXA11 transcription, which modulated SLC1A5/ASCT2 protein expression by binding competitively to miR-122-5p. The knockout of ANXA11 attenuated colorectal cancer formation in vivo. Collectively, we shed light on a closely cooperative machinery between HSF1 and super enhancers. HSF1 could stimulate acetyltransferase P300-mediated super-enhancer activity to facilitate LINC00857 expression, contributing to SLC1A5-mediated glutamine transport. Targeting the HSF1/LINC00857/ANXA11 axis may provide a valuable therapeutic strategy against colorectal cancer.

Project description:BackgroundSuper-enhancers (SEs), driving high-level expression of genes with tumor-promoting functions, have been investigated recently. However, the roles of super-enhancer-associated lncRNAs (SE-lncRNAs) in tumors remain undetermined, especially in gliomas. We here established a SE-lncRNAs expression-based prognostic signature to choose the effective treatment of glioma and identify a novel therapeutic target.MethodsCombined analysis of RNA sequencing (RNA-seq) data and ChIP sequencing (ChIP-seq) data of glioma patient-derived glioma stem cells (GSCs) screened SE-lncRNAs. Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets served to construct and validate SE-lncRNA prognostic signature. The immune profiles and potential immuno- and chemotherapies response prediction value of the signature were also explored. Moreover, we verified the epigenetic activation mechanism of LINC00945 via the ChIP assay, and its effect on glioma was determined by performing the functional assay and a mouse xenograft model.Results6 SE-lncRNAs were obtained and identified three subgroups of glioma patients with different prognostic and clinical features. A risk signature was further constructed and demonstrated to be an independent prognostic factor. The high-risk group exhibited an immunosuppressive microenvironment and was higher enrichment of M2 macrophage, regulatory T cells (Tregs), and Cancer-associated fibroblasts (CAFs). Patients in the high-risk group were better candidates for immunotherapy and chemotherapeutics. The SE of LINC00945 was further verified via ChIP assay. Mechanistically, BRD4 may mediate epigenetic activation of LINC00945. Additionally, overexpression of LINC00945 promoted glioma cell proliferation, EMT, migration, and invasion in vitro and xenograft tumor formation in vivo.ConclusionOur study constructed the first prognostic SE-lncRNA signature with the ability to optimize the choice of patients receiving immuno- and chemotherapies and provided a potential therapeutic target for glioma.

Dataset Information

Super-Enhancer LncRNA LINC00162 Promotes Progression of Bladder Cancer.

Publications

Super-Enhancer LncRNA LINC00162 Promotes Progression of Bladder Cancer.

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