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      IL-17 Affects the Progression, Metastasis, and Recurrence of Laryngeal Cancer via the Inhibition of Apoptosis through Activation of the PI3K/AKT/FAS/FASL Pathways

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          Abstract

          Background

          Cytokines play important roles in the development and prognosis of laryngeal cancer (LC). Interleukin-17 (IL-17) from a distinct subset of CD4+ T cells may significantly induce cancer-elicited inflammation to prevent tumor immune surveillance.

          Methods

          The expression levels of IL-17 were examined among 60 patients with LC. Immunofluorescence colocalization experiments were performed to verify the localization of IL-17 and FAS/FASL in Hep-2 and Tu212 cells. The role of IL-17 was determined using siRNA techniques in the LC cell line.

          Results

          In the LC patients, cytokines were dysregulated in LC tissues compared with normal tissues. It was found that IL-17 was overexpressed in a cohort of 60 LC tumors paired with nontumor tissues. Moreover, high IL-17 expression was significantly associated with the advanced T category, the late clinical stage, differentiation, lymph node metastasis, and recurrence. In addition, the time course expression of FAS and FASL was observed after stimulation and treatment with the IL-17 stimulator. Finally, in vitro experiments demonstrated that IL-17 functioned as an oncogene by inhibiting the apoptosis of LC cells via the PI3K/AKT/FAS/FASL pathways.

          Conclusions

          In summary, these findings demonstrated for the first time the role of IL-17 as a tumor promoter and a prometastatic factor in LC and indicated that IL-17 may have an oncogenic role and serve as a potential prognostic biomarker and therapeutic target in LC.

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          Most cited references59

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          Mammalian microRNAs predominantly act to decrease target mRNA levels

          Huili Guo, Nicholas Ingolia, Jonathan S Weissman … (2010)
          Summary MicroRNAs (miRNAs) are endogenous ∼22-nucleotide RNAs that play important gene-regulatory roles by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.
          Article 0 comments Cited 412 times – based on 0 reviews     Review now
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            Regulatory network of miRNA on its target: coordination between transcriptional and post-transcriptional regulation of gene expression

            Mengfan Pu, Jing Chen, Zhouteng Tao … (2019)
            MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that participate in a majority of biological processes via regulating target gene expression. The post-transcriptional repression through miRNA seed region binding to 3' UTR of target mRNA is considered as the canonical mode of miRNA-mediated gene regulation. However, emerging evidence suggests that other regulatory modes exist beyond the canonical mechanism. In particular, the function of intranuclear miRNA in gene transcriptional regulation is gradually revealed, with evidence showing their contribution to gene silencing or activating. Therefore, miRNA-mediated regulation of gene transcription not only expands our understanding of the molecular mechanism underlying miRNA regulatory function, but also provides new evidence to explain its ability in the sophisticated regulation of many bioprocesses. In this review, mechanisms of miRNA-mediated gene transcriptional and post-transcriptional regulation are summarized, and the synergistic effects among these actions which form a regulatory network of a miRNA on its target are particularly elaborated. With these discussions, we aim to emphasize the importance of miRNA regulatory network on target gene regulation and further highlight the potential application of the network mode in the achievement of a more effective and stable modulation of the target gene expression.
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              The expanding RNA polymerase III transcriptome.

              Martin Teichmann, Aldo Pagano, Giorgio Dieci … (2007)
              The role of RNA polymerase (Pol) III in eukaryotic transcription is commonly thought of as being restricted to a small set of highly expressed, housekeeping non-protein-coding (nc)RNA genes. Recent studies, however, have remarkably expanded the set of known Pol III-synthesized ncRNAs, suggesting that gene-specific Pol III regulation is more common than previously appreciated. Newly identified Pol III transcripts include small nucleolar RNAs, microRNAs, short interspersed nuclear element-encoded or tRNA-derived RNAs and novel classes of ncRNA that can display significant sequence complementarity to protein-coding genes and might thus regulate their expression. The extent of the Pol III transcriptome, the complexity of its regulation and its influence on cell physiology, development and disease are emerging as new areas for future research.
              Article 0 comments Cited 72 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Yan Sun:
                ORCID: https://orcid.org/0000-0002-8564-925X
                Jianming Yang:
                ORCID: https://orcid.org/0000-0002-2823-7339
                Journal
                Journal ID (nlm-ta): J Immunol Res
                Journal ID (iso-abbrev): J Immunol Res
                Journal ID (publisher-id): JIR
                Title: Journal of Immunology Research
                Publisher: Hindawi
                ISSN (Print): 2314-8861
                ISSN (Electronic): 2314-7156
                Publication date Collection: 2020
                Publication date (Electronic): 18 December 2020
                Volume: 2020
                Electronic Location Identifier: 2953191
                Affiliations
                1Department of Otorhinolaryngology, The Second Hospital of Anhui Medical University, Hefei, Anhui 230601, China
                2Department of Otorhinolaryngology and Head and Neck Surgery, Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China
                3Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing 100730, China
                4Physical Examination Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
                5Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, China
                Author notes

                Academic Editor: Luis Alberto Ponce-Soto

                Author information
                https://orcid.org/0000-0002-4333-8103
                https://orcid.org/0000-0002-3235-7405
                https://orcid.org/0000-0001-7314-4070
                https://orcid.org/0000-0002-8564-925X
                https://orcid.org/0000-0001-5862-9520
                https://orcid.org/0000-0001-9218-7826
                https://orcid.org/0000-0002-1352-7296
                https://orcid.org/0000-0002-5044-4086
                https://orcid.org/0000-0002-2823-7339
                Article
                DOI: 10.1155/2020/2953191
                PMC ID: 7769679
                PubMed ID: 33415169
                SO-VID: f3c60296-f9f7-4e20-a950-62e8a2e8daea
                Copyright © Copyright © 2020 Yang Song et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 8 July 2020
                Date revision received : 6 October 2020
                Date accepted : 4 December 2020
                Funding
                Funded by: Natural Science Foundation of Anhui Province
                Award ID: 2008085QH423
                Categories
                Subject: Research Article

                Data availability:

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