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      A systematic framework for identifying prognostic necroptosis-related lncRNAs and verification of lncRNA CRNDE/miR-23b-3p/IDH1 regulatory axis in glioma

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          Abstract

          Glioma remains the most frequent malignancy of the central nervous system. Recently, necroptosis has been identified as a cell death process that mediates the proliferation and development of tumor cells. LncRNAs play a key role in the diagnosis and treatment of various diseases. However, the impact that necrosis-related lncRNAs (NRLs) have on glioma remains unclear. In our studies, we selected 9 NRLs to construct a prognostic model. Meanwhile, we assessed the survival curves of these 9 NRLs. Our findings found ADGRA1-AS1 and WAC-AS1 were protective lncRNAs, while MIR210HG, LINC01503, CRNDE, HOXC-AS1, ZIM2-AS1, MIR22HG and PLBD1-AS1 were risk lncRNAs. Specifically, 12 immune cells, 25 immune-correlated pathways, and TME score were differentially expressed in the both risk groups. Additionally, the study predicted and validated the necroptosis-related lncRNA CRNDE/miR-23b-3p/IDH1 axis. CRNDE was strongly expressed in glioma specimens and several cell lines. Inhibiting CRNDE resulted in a substantial reduction in the proliferation and migration of U-118MG and U251 cells. Furthermore, the study predicted that CRNDE may exhibit oncogenic features by adsorbing miR-23b-3p and positively regulating IDH1 expression. Overall, the study constructed a prognostic model in glioma, and predicted a lncRNA CRNDE/miR-23b-3p/IDH1 axis, which could potentially be useful for gene therapy of glioma.

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          Tumor microenvironment and therapeutic response

          The tumor microenvironment significantly influences therapeutic response and clinical outcome. Microenvironment-mediated drug resistance can be induced by soluble factors secreted by tumor or stromal cells. The adhesion of tumor cells to stromal fibroblasts or to components of the extracellular matrix can also blunt therapeutic response. Microenvironment-targeted therapy strategies include inhibition of the extracellular ligand-receptor interactions and downstream pathways. Immune cells can both improve and obstruct therapeutic efficacy and may vary in their activation status within the tumor microenvironment; thus, re-programme of the immune response would be substantially more beneficial. The development of rational drug combinations that can simultaneously target tumor cells and the microenvironment may represent a solution to overcome therapeutic resistance.
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            LncRNA-mediated regulation of cell signaling in cancer

            To date, a large number of long non-coding RNAs (lncRNAs) have been recently discovered through functional genomics studies. Importantly, lncRNAs have been shown, in many cases, to function as master regulators for gene expression and thus, they can play a critical role in various biological functions and disease processes including cancer. Although the lncRNA-mediated gene expression involves various mechanisms, such as regulation of transcription, translation, protein modification, and the formation of RNA-protein or protein-protein complexes, in this review we discuss the latest developments primarily in important cell signaling pathways regulated by lncRNAs in cancer.
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              Tumor microenvironment as a therapeutic target in cancer

              Tumor microenvironment denotes the non-cancerous cells and components presented in the tumor, including molecules produced and released by them. The constant interactions between tumor cells and the tumor microenvironment play decisive roles in tumor initiation, progression, metastasis, and response to therapies. The tumor microenvironment as a therapeutic target in cancer has attracted great research and clinical interest. Here we summarize the current progress in targeting the tumor microenvironment in both drug development and clinical trials; highlight challenges in targeting the tumor microenvironment to achieve therapeutic efficacy; explore new technologies and approaches to better decipher the tumor microenvironment; and discuss strategies to intervene in the pro-tumor microenvironment and maximize therapeutic benefits.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                15 November 2023
                06 November 2023
                : 15
                : 21
                : 12296-12313
                Affiliations
                [1 ]Department of Dermatology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
                [2 ]Department of Dermatology, Dermatology Hospital, Southern Medical University, Guangzhou, China
                [3 ]Department of Neurology and Stroke Centre, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
                [4 ]Department of Traditional Chinese Medicine, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Ling Jin; email: jinlingjnu@foxmail.com, https://orcid.org/0009-0002-6441-5515
                Article
                205180 205180
                10.18632/aging.205180
                10683586
                37934582
                8fe515d8-3193-46f0-b6b9-2a261397b14f
                Copyright: © 2023 Chen et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 31 May 2023
                : 26 September 2023
                Categories
                Research Paper

                Cell biology
                glioma,necroptosis,lncrna crnde,mir-23b-3p,idh1
                Cell biology
                glioma, necroptosis, lncrna crnde, mir-23b-3p, idh1

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