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      A novel circRNA, circNUP98, a potential biomarker, acted as an oncogene via the miR‐567/ PRDX3 axis in renal cell carcinoma

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          Abstract

          In recent years, plenty of studies found that circular RNAs (circRNAs) were essential players in the initiation and progression of various cancers including the renal cell carcinoma (RCC). However, the knowledge about the circRNAs in carcinogenesis is still limited. Dysregulated expression of circNUP98 in RCC tissues was identified by the circular RNA microarray. RT‐PCR was performed to measure the expression of circNUP98 in 78 pairs of RCC tissues and adjacent normal tissues. Survival analysis was conducted to explore the association between the expression of circNUP98 and the prognosis of RCC. The function and underlying mechanisms of circSMC3 in RCC cells were investigated by RNAi, CCK‐8, Western blotting, bioinformatic analysis, ChIP assay, circRIP assay and dual luciferase reporter assay. CircNUP98 was up‐regulated in both RCC tissues and cell lines, and high expression of circNUP98 was correlated with poor prognosis of RCC patients. Silencing of circSMC3 inhibited the proliferation and promoted the apoptosis in a caspase‐dependent manner in RCC cells. Mechanistically, we revealed that silencing of circ NUP98 inhibited RCC progression by down‐regulating of PRDX3 via up‐regulation of miR‐567. Furthermore, STAT3 was identified as an inducer of circ NUP98 in RCC cells. CircNUP98 acts as an oncogene by a novel STAT3/circ NUP98/miR‐567/PRDX3 axis, which may provide a potential biomarker and therapeutic target for the treatment of RCC.

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          Origins and Mechanisms of miRNAs and siRNAs.

          Richard W. Carthew, Erik J. Sontheimer (2009)
          Over the last decade, approximately 20-30 nucleotide RNA molecules have emerged as critical regulators in the expression and function of eukaryotic genomes. Two primary categories of these small RNAs--short interfering RNAs (siRNAs) and microRNAs (miRNAs)--act in both somatic and germline lineages in a broad range of eukaryotic species to regulate endogenous genes and to defend the genome from invasive nucleic acids. Recent advances have revealed unexpected diversity in their biogenesis pathways and the regulatory mechanisms that they access. Our understanding of siRNA- and miRNA-based regulation has direct implications for fundamental biology as well as disease etiology and treatment.
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            Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling.

            David G Cox, Christine Winterbourn, Nicholas B Hampton (2010)
            Prxs (peroxiredoxins) are a family of proteins that are extremely effective at scavenging peroxides. The Prxs exhibit a number of intriguing properties that distinguish them from conventional antioxidants, including a susceptibility to inactivation by hyperoxidation in the presence of excess peroxide and the ability to form complex oligomeric structures. These properties, combined with a high cellular abundance and reactivity with hydrogen peroxide, have led to speculation that the Prxs function as redox sensors that transmit signals as part of the cellular response to oxidative stress. Multicellular organisms express several different Prxs that can be categorized by their subcellular distribution. In mammals, Prx 3 and Prx 5 are targeted to the mitochondrial matrix. Mitochondria are a major source of hydrogen peroxide, and this oxidant is implicated in the damage associated with aging and a number of pathologies. Hydrogen peroxide can also act as a second messenger, and is linked with signalling events in mitochondria, including the induction of apoptosis. A simple kinetic competition analysis estimates that Prx 3 will be the target for up to 90% of hydrogen peroxide generated in the matrix. Therefore, mitochondrial Prxs have the potential to play a major role in mitochondrial redox signalling, but the extent of this role and the mechanisms involved are currently unclear.
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              Genome-wide profiling of Sus scrofa circular RNAs across nine organs and three developmental stages

              Guoming Liang, Yalan Yang, Guanglin Niu … (2017)
              Abstract The spatio-temporal expression patterns of Circular RNA (circRNA) across organs and developmental stages are critical for its function and evolution analysis. However, they remain largely unclear in mammals. Here, we comprehensively analysed circRNAs in nine organs and three skeletal muscles of Guizhou miniature pig (S. scrofa), a widely used biomedical model animal. We identified 5,934 circRNAs and analysed their molecular properties, sequence conservation, spatio-temporal expression pattern, potential function, and interaction with miRNAs. S. scrofa circRNAs show modest sequence conservation with human and mouse circRNAs, are flanked by long introns, exhibit low abundance, and are expressed dynamically in a spatio-temporally specific manner. S. scrofa circRNAs show the greatest abundance and complexity in the testis. Notably, 31% of circRNAs harbour well-conserved canonical miRNA seed matches, suggesting that some circRNAs act as miRNAs sponges. We identified 149 circRNAs potentially associated with muscle growth and found that their host genes were significantly involved in muscle development, contraction, chromatin modification, cation homeostasis, and ATP hydrolysis-coupled proton transport; moreover, this set of genes was markedly enriched in genes involved in tight junctions and the calcium signalling pathway. Finally, we constructed the first public S. scrofa circRNA database, allowing researchers to query comprehensive annotation, expression, and regulatory networks of circRNAs.
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                Author and article information

                Contributors
                Yu Ren:
                ORCID: https://orcid.org/0000-0003-1154-4487
                nbrenyu@163.com
                Journal
                Journal ID (nlm-ta): J Cell Mol Med
                Journal ID (iso-abbrev): J. Cell. Mol. Med
                Journal ID (doi): 10.1111/(ISSN)1582-4934
                Journal ID (publisher-id): JCMM
                Title: Journal of Cellular and Molecular Medicine
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1582-1838
                ISSN (Electronic): 1582-4934
                Publication date (Electronic): 30 July 2020
                Publication date (Print): September 2020
                Volume: 24
                Issue: 17 ( doiID: 10.1111/jcmm.v24.17 )
                Pages: 10177-10188
                Affiliations
                [ 1 ] Zhejiang Key Laboratory of Pathophysiology Department of Biochemistry and Molecular Biology Medical School Ningbo University Ningbo China
                [ 2 ] School of Marine Science Ningbo University Ningbo China
                [ 3 ] Department of Urologic Surgery Ningbo Urology and Nephrology Hospital, Ningbo Yinzhou NO2. Hospital Ningbo China
                Author notes
                [*] [* ] Correspondence

                Yu Ren, Department of Urologic Surgery, Ningbo Urology and Nephrology Hospital, 1 Qianhe Road, Ningbo, Zhejiang 315000, China.

                Email: nbrenyu@ 123456163.com

                Author information
                https://orcid.org/0000-0003-2330-6937
                https://orcid.org/0000-0003-1154-4487
                Article
                Publisher ID: JCMM15629
                DOI: 10.1111/jcmm.15629
                PMC ID: 7520319
                PubMed ID: 32729669
                SO-VID: 69c4f7d6-6d34-44d0-9382-dd6dd1a62b31
                Copyright © © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 10 May 2020
                Date revision received : 11 June 2020
                Date accepted : 19 June 2020
                Page count
                Figures: 7, Tables: 1, Pages: 12, Words: 6901
                Categories
                Subject: Original Article
                Subject: Original Articles
                Custom metadata
                source-schema-version-number 2.0
                cover-date September 2020
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.1 mode:remove_FC converted:27.09.2020

                ScienceOpen disciplines: Molecular medicine
                Keywords: circnup98,mir‐567,prdx3,renal cell carcinoma
                Data availability:
                ScienceOpen disciplines: Molecular medicine
                Keywords: circnup98, mir‐567, prdx3, renal cell carcinoma

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