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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Novel Tumor Suppressor lncRNA Growth Arrest-Specific 5 (GAS5) In Human Cancer

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      OncoTargets and therapy
      Dove
      GAS5, cancer, tumor suppressor, biomarker, therapeutic target

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          Abstract

          Long noncoding RNAs (lncRNAs) play crucial regulatory roles in fundamental biological processes, and deregulations of lncRNAs have been linked to numerous human diseases, especially cancers. Of particular interest in this regard is lncRNA GAS5, which is mainly identified as a tumor suppressor in several cancers. GAS5 was significantly low expressed in multiple cancers and was associated with clinic-pathological characteristics and patient survival, indicating a novel potential diagnostic and prognostic biomarker, and a therapeutic target for cancer. Functionally, GAS5 is involved in cell proliferation, metastasis, invasion, apoptosis, epithelial–mesenchymal transition (EMT), and drug resistance, among others, via multiple molecular mechanisms, such as binding to DNA sequences, forming RNA–DNA triplex complex, triggering or suppressing the expression of genes, binding proteins to form chromatin-modifying complex, which activates or represses gene expression, and acting as miRNA sponge to suppress miRNA expression, leading to regulation of miRNA target genes. This review provides an overview of the current state of knowledge and role of GAS5 in clinical relevance, biological functions and molecular mechanisms underlying the dysregulation of expression and function of GAS5 in cancer. Finally, the potential prospective role as diagnostic and prognostic biomarker and therapeutic target in cancer is discussed.

          Most cited references118

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          GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer.

          Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.
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            Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma

            Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.
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              Genes specifically expressed at growth arrest of mammalian cells.

              A subtraction cDNA library enriched for RNA sequences preferentially expressed in growth-arrested cells was prepared. Six cDNA clones were identified, varying in abundance from 2% to 0.0002% of the library and in size from 0.8 to 10 kb. The corresponding mRNAs are downregulated with different kinetics upon induction of growth by serum. The kinetics of induction after serum starvation and density-dependent inhibition of two of these growth-arrest-specific (gas) genes were investigated in more detail. Two cell lines transformed by viral onc genes did not express the two gas genes. The full-length cDNA for one gene has been sequenced and the protein product preliminarily characterized by in vitro translation.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OTT
                ott
                OncoTargets and therapy
                Dove
                1178-6930
                11 October 2019
                2019
                : 12
                : 8421-8436
                Affiliations
                [1 ]Laboratory of Tumor Biology, The Second Clinical Collage of Guangzhou University of Chinese Medicine , Guangzhou, Guangdong Province 510120, People’s Republic of China
                Author notes
                Correspondence: Swei Sunny Hann Laboratory of Tumor Biology, The Second Clinical Collage of Guangzhou University of Chinese Medicine , No. 111, Dade Road, Guangzhou, Guangdong Province510120, People’s Republic of ChinaTel +86 020-39318472 Email hann2012@outlook.com
                Author information
                http://orcid.org/0000-0003-2030-5285
                Article
                221305
                10.2147/OTT.S221305
                6794681
                31632088
                bff077bc-7c82-49fe-ba52-43c8be85c479
                © 2019 Yu and Hann.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 29 June 2019
                : 24 September 2019
                Page count
                Figures: 2, Tables: 3, References: 153, Pages: 16
                Categories
                Review

                Oncology & Radiotherapy
                gas5,cancer,tumor suppressor,biomarker,therapeutic target
                Oncology & Radiotherapy
                gas5, cancer, tumor suppressor, biomarker, therapeutic target

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