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      The regulatory relationship between transcription factor STAT3 and noncoding RNA

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          Abstract

          Signal transducer and activator of transcription 3 (STAT3), as a key node in numerous carcinogenic signaling pathways, is activated in various tumor tissues and plays important roles in tumor formation, metastasis, and drug resistance. STAT3 is considered a potential subtarget for tumor therapy. Noncoding RNA (ncRNA) is a special type of RNA transcript. Transforming from “junk” transcripts into key molecules involved in cell apoptosis, growth, and functional regulation, ncRNA has been proven to be closely related to various epithelial–mesenchymal transition and drug resistance processes in tumor cells over the past few decades. Research on the relationship between transcription factor STAT3 and ncRNAs has attracted increased attention. To date, existing reviews have mainly focused on the regulation by ncRNAs on the transcription factor STAT3; there has been no review of the regulation by STAT3 on ncRNAs. However, understanding the regulation of ncRNAs by STAT3 and its mechanism is important to comprehensively understand the mutual regulatory relationship between STAT3 and ncRNAs. Therefore, in this review, we summarize the regulation by transcription factor STAT3 on long noncoding RNA, microRNA, and circular RNA and its possible mechanisms. In addition, we provide an update on research progress on the regulation of STAT3 by ncRNAs. This will provide a new perspective to comprehensively understand the regulatory relationship between transcription factor STAT3 and ncRNAs, as well as targeting STAT3 or ncRNAs to treat diseases such as tumors.

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          Most cited references131

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          The Role of Non-coding RNAs in Oncology

          For decades, research into cancer biology focused on the involvement of protein-coding genes. Only recently was it discovered that an entire class of molecules, termed non-coding RNA (ncRNA), plays key regulatory roles in shaping cellular activity. An explosion of studies into ncRNA biology has since shown that they represent a diverse and prevalent group of RNAs including both oncogenic molecules and those that work in a tumor suppressive manner. As a result, hundreds of cancer-focused clinical trials involving ncRNAs as novel biomarkers or therapies have begun, and these are likely just the beginning. Slack and Chinnaiyan explore the diverse and context-dependent roles of ncRNAs, including circRNAs, lncRNAs, miRNAs, piRNAs, and tsRNAs, in cancer. They provide insight into the prospect of therapeutic targeting and use of ncRNAs as biomarkers with an up-to-date summary of clinical and preclinical studies.
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            Revisiting STAT3 signalling in cancer: new and unexpected biological functions.

            The Janus kinases (JAKs) and signal transducer and activator of transcription (STAT) proteins, particularly STAT3, are among the most promising new targets for cancer therapy. In addition to interleukin-6 (IL-6) and its family members, multiple pathways, including G-protein-coupled receptors (GPCRs), Toll-like receptors (TLRs) and microRNAs were recently identified to regulate JAK-STAT signalling in cancer. Well known for its role in tumour cell proliferation, survival, invasion and immunosuppression, JAK-STAT3 signalling also promotes cancer through inflammation, obesity, stem cells and the pre-metastatic niche. In addition to its established role as a transcription factor in cancer, STAT3 regulates mitochondrion functions, as well as gene expression through epigenetic mechanisms. Newly identified regulators and functions of JAK-STAT3 in tumours are important targets for potential therapeutic strategies in the treatment of cancer.
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              Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells.

              Glioblastoma multiforme (GBM) displays cellular hierarchies harboring a subpopulation of stem-like cells (GSCs). Enhancer of Zeste Homolog 2 (EZH2), the lysine methyltransferase of Polycomb repressive complex 2, mediates transcriptional repression of prodifferentiation genes in both normal and neoplastic stem cells. An oncogenic role of EZH2 as a transcriptional silencer is well established; however, additional functions of EZH2 are incompletely understood. Here, we show that EZH2 binds to and methylates STAT3, leading to enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3. The EZH2-STAT3 interaction preferentially occurs in GSCs relative to non-stem bulk tumor cells, and it requires a specific phosphorylation of EZH2. Inhibition of EZH2 reverses the silencing of Polycomb target genes and diminishes STAT3 activity, suggesting therapeutic strategies. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                zhouyanhong@csu.edu.cn
                liyanling@hnca.org.cn
                Journal
                Cell Mol Biol Lett
                Cell Mol Biol Lett
                Cellular & Molecular Biology Letters
                BioMed Central (London )
                1425-8153
                1689-1392
                3 January 2024
                3 January 2024
                2024
                : 29
                : 4
                Affiliations
                [1 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Department of Nuclear Medicine, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, , Central South University, ; Changsha, 410013 China
                [2 ]Cancer Research Institute, Basic School of Medicine, Central South University, ( https://ror.org/00f1zfq44) Changsha, 410011 Hunan China
                Author information
                http://orcid.org/0000-0002-9498-4439
                Article
                521
                10.1186/s11658-023-00521-1
                10763091
                38172648
                9f73a379-ba9b-48f4-84ca-e9e45ce3f50b
                © The Author(s) 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 September 2023
                : 12 December 2023
                Funding
                Funded by: the National Natural Sciences Foundation of China
                Award ID: 82273219
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004735, Natural Science Foundation of Hunan Province;
                Award ID: 2021JJ30915
                Award Recipient :
                Categories
                Mini Review
                Custom metadata
                © University of Wroclav 2024

                circrna,lncrna,microrna,stat3,transcription factor
                circrna, lncrna, microrna, stat3, transcription factor

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