Dataset Information

Long Noncoding RNA GM16343 Promotes IL-36? to Regulate Tumor Microenvironment by CD8+T cells.

ABSTRACT: OBJECTIVE:To investigate the effect of long noncoding RNA GM16343 on interleukin 36? promotion of CD8+T cells in tumor microenvironment regulation. METHODS:The differentially expressed long noncoding RNA in interleukin 36?-stimulated mouse CD8+T cells was screened by gene chip technology, and the significant differentially expressed long noncoding RNAs were verified by real-time polymerase chain reaction. The lentiviral vector that overexpresses or knockdown GM16343 was constructed, transfected into CD8+T cells, and stimulated with interleukin 36?, and the amount of interferon ? secreted was detected by enzyme-linked immunosorbent assay. A mouse subcutaneous xenograft model that stably express interleukin 36? was established, and the tumor size and mouse survival time were observed by stimulation with CD8+T cells overexpression or knockdown of GM16343. RESULTS:A total of 12 long noncoding RNAs with significant differences were screened by gene chip analysis. Real-time polymerase chain reaction showed that the difference in GM16343 was larger, and the difference between the groups was observed to be the most significant. Compared to control group, CD8+T cells overexpressing GM16343 increased the secretion of interferon ?, and the tumor diameter of the mice after stimulation showed significant reduction, and the survival time showed significant prolongation. Compared to control group, the CD8+T cells after GM16343 were knocked down. The interferon ? secretion was decreased, and no significant change in tumor diameter and survival time was observed. CONCLUSION:Interleukin 36? may enhance antitumor immune response of CD8+T cells by regulating GM16343.

SUBMITTER: Mao D

PROVIDER: S-EPMC6831968 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

Long Noncoding RNA GM16343 Promotes IL-36β to Regulate Tumor Microenvironment by CD8<sup>+</sup>T cells.

Mao Deli D Hu Chenrui C Zhang Jianglei J Feng Chao C Zhang Zhe Z Wang Jin J Man Zhongsong Z Zhu Zhongwei Z Wang Yunliang Y Zhao Hua H Zhu Xinguo X Ouyang Jun J Dong Xiaoqiang X Zhao Xin X

Technology in cancer research & treatment 20190101

<h4>Objective</h4>To investigate the effect of long noncoding RNA GM16343 on interleukin 36β promotion of CD8<sup>+</sup>T cells in tumor microenvironment regulation.<h4>Methods</h4>The differentially expressed long noncoding RNA in interleukin 36β-stimulated mouse CD8<sup>+</sup>T cells was screened by gene chip technology, and the significant differentially expressed long noncoding RNAs were verified by real-time polymerase chain reaction. The lentiviral vector that overexpresses or knockdown ...[more]

PMID: 31684829

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Project description:BackgroundThyroid cancer (TC) is a rapidly increasing incidence of endocrine malignancies, occupying 3% of new cancer incidence, of which 10% has a heterogeneous prognosis. Ferroptosis is a form of cell death distinct from apoptosis, which involves antitumor drug-related research. Long noncoding RNAs (lncRNAs) could affect cancer prognosis by regulating the ferroptosis; thus, ferroptosis-associated lncRNAs are emerging as prospective biomarkers for cancer therapy and prognosis. However, the prognostic factors of ferroptosis-associated lncRNAs in this solid tumor and their mechanisms remain unknown.MethodsThe TC lncRNA data were extracted from RNA sequencing files of The Cancer Genome Atlas (TCGA). Then, we performed a two-cluster analysis and grouped 502 patients with TC in a 7 : 3 ratio. Both the least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis were conducted to create and validate the ferroptosis-associated lncRNA prognostic model (Ferr-LPM). Based on the median Ferr-LPM-based risk score (LPM_score) of the training cohort, we categorized patients into high and low LPM_score groups, which were then subjected to prognostic correlation and difference analysis. We also created a nomogram and assessed its predictive ability. Furthermore, immune-related mechanisms were investigated by analyzing the tumor immune microenvironment (TIME) and applying algorithms such as CIBERSROT.ResultsWe built a highly accurate nomogram to promote the clinical applicability of Ferr-LPM. The area under the receiver operating characteristic curve (AUC-ROC) reached above 0.9. Survival analysis suggested that when the Ferr-LPM score was higher, the overall survival (OS) of patients within this group was shorter. Meanwhile, we found a strong association between Ferr-LPM and TIME. Interestingly, the LPM_score was inversely proportional to the tumor purity but positively related to immune checkpoint blockade (ICB) response.ConclusionWe constructed a novel ferroptosis-associated lncRNA nomogram that could highly predict the prognosis of TC patients. Ferroptosis-associated lncRNAs might possess potential functions in regulating TIME, and lncRNAs provide TC patients with new prognostic biomarkers and therapeutic targets.

Dataset Information

Long Noncoding RNA GM16343 Promotes IL-36? to Regulate Tumor Microenvironment by CD8+T cells.

Publications

Long Noncoding RNA GM16343 Promotes IL-36β to Regulate Tumor Microenvironment by CD8<sup>+</sup>T cells.

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