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      GAS5-mediated regulation of cell signaling

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          Abstract

          In recent years, an increasing number of long non-coding RNAs (lncRNAs) have been discovered using microarrays and nucleic acid sequencing technology. LncRNAs exert crucial biological functions by regulating signaling pathways. In particular, the lncRNA growth arrest-specific transcript 5 (GAS5) has been documented to serve a crucial role in numerous signaling pathways. This article discusses the latest developments in the association between GAS5 and microRNA (miRNA), p53, mTOR, glucocorticoid response element (GRE) and AKT in order to investigate the roles served by GAS5. miRNAs can activate related signaling pathways and GAS5 can combine with miRNA to regulate related signaling pathways. GAS5 may regulate p53 expression via derivation of snoRNA, but the underlying mechanism requires further investigation. GAS5 overxpresion reduces the expression level of mTOR, which is induced by inhibiting miR-106a-5p expression. GAS5 is a sponge of GR, and serves a role in controlling and maintaining glucocorticoid sensitivity and drug resistance via competitive combination with GR. GAS5 can interact with miRNAs, such as miR-21 and miR-532-5p, to regulate the expression of AKT signaling pathway, affecting cell survival and apoptosis. Collectively, the data indicate that GAS5 serves a key role in the miRNA, p53, mTOR, GRE, and AKT signaling pathways. GAS5 regulates complex intracellular signaling pathways primarily through three modes of action, all of which are interrelated: Signal, decoy and guide. In the present article, latest developments in the association between GAS5 and a number of cellular signaling pathways are discussed to examine the tumor suppressive role of GAS5.

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          Most cited references68

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          mTOR signaling pathway and mTOR inhibitors in cancer: progress and challenges

          Mammalian target of rapamycin (mTOR) regulates cell proliferation, autophagy, and apoptosis by participating in multiple signaling pathways in the body. Studies have shown that the mTOR signaling pathway is also associated with cancer, arthritis, insulin resistance, osteoporosis, and other diseases. The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism. Therefore, the mTOR signaling pathway is a hot target in anti-tumor therapy research. In recent years, a variety of newly discovered mTOR inhibitors have entered clinical studies, and a variety of drugs have been proven to have high activity in combination with mTOR inhibitors. The purpose of this review is to introduce the role of mTOR signaling pathway on apoptosis, autophagy, growth, and metabolism of tumor cells, and to introduce the research progress of mTOR inhibitors in the tumor field.
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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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              Long noncoding RNAs and exosomal lncRNAs: classification, and mechanisms in breast cancer metastasis and drug resistance

              Breast cancer is the most common cancer, and the second cause of cancer-related deaths (after lung cancer) among women. Developing tumor metastasis and invasion is the most important cause of death in breast cancer patients. Several key factors participate in breast cancer metastasis including long noncoding RNAs (lncRNAs). lncRNAs are a category of cellular RNAs that are longer than 200 nucleotides in length. Accumulating evidence suggests that lncRNAs have the potential to be promising diagnostic, prognostic biomarkers and therapeutic targets in breast cancer. Understanding the role of lncRNAs and their mechanisms of functions might help to further discovery of breast cancer biological characteristics. In this review, we discuss physiological functions, epigenetic regulation, transcriptional regulation of lncRNAs, and their important role in tumor progression and metastasis. Some lncRNAs function as oncogenes and some function as tumor suppressors. Interestingly, recent reports depict that hypomethylation of promoters of lncRNAs play a pivotal role in cancer progression, suggesting the importance of epigenetic regulation. Furthermore, we discuss the role of lncRNAs in exosomes and their function in drug resistance, and therapeutic importance of exosomal lncRNAs in cancer biology. In summary, lncRNAs have a great potential to consider them as novel prognostic biomarkers as well as new therapeutic targets in breast cancer.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                October 2020
                19 August 2020
                19 August 2020
                : 22
                : 4
                : 3049-3056
                Affiliations
                Department of Urology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212000, P.R. China
                Author notes
                Correspondence to: Dr Binghai Chen, Department of Urology, Affiliated Hospital of Jiangsu University, 438 Jiefang Road, Zhenjiang, Jiangsu 212000, P.R. China, E-mail: chenbhny@ 123456163.com
                Article
                MMR-22-04-3049
                10.3892/mmr.2020.11435
                7453608
                32945519
                bcc9302a-37d3-4339-9c75-3000dbead7ae
                Copyright: © Zhou et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 15 February 2020
                : 19 June 2020
                Categories
                Review

                long non-coding rnas,growth arrest-specific transcript 5,cellular signaling pathway

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