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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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      Curcumin suppresses the progression of laryngeal squamous cell carcinoma through the upregulation of miR-145 and inhibition of the PI3K/Akt/mTOR pathway

      research-article
      1 , 2
      OncoTargets and therapy
      Dove Medical Press
      curcumin, miR-145, the PI3K/Akt/mTOR pathway, LSCC

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          Abstract

          Background

          Curcumin is a polyphenol extracted from the rhizomes of Curcuma longa with extensive biological and pharmacological effects. The present study aimed to investigate the mechanisms of curcumin in laryngeal squamous cell carcinoma (LSCC).

          Methods

          Quantitative real-time reverse transcriptase-polymerase chain reaction was performed to detect the expressions of miR-145 in LSCC tissues and cells. The effects of miR-145 and curcumin on cell proliferation, apoptosis, cell cycle, migration and invasion were explored by MTT assay, flow cytometry analysis, Transwell migration and invasion assay, respectively. The effects of miR-145 combined with curcumin on the phosphoinositol 1,3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway were detected by Western blot analysis.

          Results

          miR-145 was significantly downregulated in LSCC tissues and cells. Curcumin administration upregulated miR-145 expression in LSCC cells in a dose-dependent manner. miR-145 overexpression and curcumin treatment both markedly suppressed cell proliferation, migration and invasion and induced cell cycle arrest and apoptosis in LSCC cells. Moreover, curcumin treatment reversed the enhanced effects on cell viability, migration and invasion and the inhibitory effects on apoptosis conferred by anti-miR-145 in LSCC cells. Curcumin treatment dramatically aggravated miR-145-induced inhibition of the PI3K/Akt/mTOR pathway and reversed anti-miR-145-mediated activation of the PI3K/Akt/mTOR pathway in LSCC cells.

          Conclusion

          Curcumin suppressed LSCC progression through the upregulation of miR-145 and inhibition of the PI3K/Akt/mTOR pathway.

          Most cited references32

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          MicroRNA—implications for cancer

          MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression post-transcriptionally. After the discovery of the first miRNA in the roundworm Caenorhabditis elegans, these short regulatory RNAs have been found to be an abundant class of RNAs in plants, animals, and DNA viruses. About 3% of human genes encode for miRNAs, and up to 30% of human protein coding genes may be regulated by miRNAs. MicroRNAs play a key role in diverse biological processes, including development, cell proliferation, differentiation, and apoptosis. Accordingly, altered miRNA expression is likely to contribute to human disease, including cancer. This review will summarize the emerging knowledge of the connections between human miRNA biology and different aspects of carcinogenesis. Various techniques available to investigate miRNAs will also be discussed.
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            The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients

            The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis plays a central role in cell proliferation, growth, and survival under physiological conditions. However, aberrant PI3K/Akt/mTOR signaling has been implicated in many human cancers, including acute myelogenous leukemia (AML). Therefore, the PI3K/Akt/mTOR network is considered as a validated target for innovative cancer therapy. The limit of acceptable toxicity for standard polychemotherapy has been reached in AML. Novel therapeutic strategies are therefore needed. This review highlights how the PI3K/Akt/mTOR signaling axis is constitutively active in AML patients, where it affects survival, proliferation, and drug-resistance of leukemic cells including leukemic stem cells. Effective targeting of this pathway with small molecule kinase inhibitors, employed alone or in combination with other drugs, could result in the suppression of leukemic cell growth. Furthermore, targeting the PI3K/Akt/mTOR signaling network with small pharmacological inhibitors, employed either alone or in combinations with other drugs, may result in less toxic and more efficacious treatment of AML patients. Efforts to exploit pharmacological inhibitors of the PI3K/Akt/mTOR cascade which show efficacy and safety in the clinical setting are now underway.
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              Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer.

              Curcumin has promising potential in cancer prevention and therapy by interacting with proteins and modifying their expression and activity, which includes transcription factors, inflammatory cytokines and factors of cell survival, proliferation and angiogenesis. miR-21 is overexpressed in many tumours, promoting progression and metastasis. In the present study, we examined the potential of curcumin to regulate miR-21, tumour growth, invasion and in vivo metastasis in colorectal cancer. In Rko and HCT116 cells, we identified two new transcriptional start sites of the miR-21 gene and delineated its promoter region. PMA stimulation induced miR-21 expression via motifs bound with AP-1 (activator protein 1) transcription factors. Curcumin treatment reduced miR-21 promoter activity and expression in a dose-dependent manner by inhibiting AP-1 binding to the promoter, and induced the expression of the tumour suppressor Pdcd4 (programmed cell death protein 4), which is a target of miR-21. Curcumin-treated Rko and HCT116 cells were arrested in the G2/M phase with increasing concentrations. Furthermore, curcumin inhibited tumour growth, invasion and in vivo metastasis in the chicken-embryo-metastasis assay [CAM (chorionallantoic membrane) assay]. Additionally, curcumin significantly inhibited miR-21 expression in primary tumours generated in vivo in the CAM assay by Rko and HCT116 cells (P<0.00006 and P<0.035 respectively). Taken together, this is the first paper to show that curcumin inhibits the transcriptional regulation of miR-21 via AP-1, suppresses cell proliferation, tumour growth, invasion and in vivo metastasis, and stabilizes the expression of the tumour suppressor Pdcd4 in colorectal cancer.
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                Author and article information

                Journal
                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                1178-6930
                2018
                19 June 2018
                : 11
                : 3521-3531
                Affiliations
                [1 ]Department of Otorhinolaryngology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou 450000, People’s Republic of China
                [2 ]Department of Otorhinolaryngology, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, People’s Republic of China
                Author notes
                Correspondence: Xiaofeng Zhu, Department of Otorhinolaryngology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, No 195 Tongbai Street, Zhongyuan District, Zhengzhou 450000, People’s Republic of China, Tel +86 371 6769 0000, Email zhuxiaofengxf126@ 123456163.com
                [*]

                These authors contributed equally to this work

                Article
                ott-11-3521
                10.2147/OTT.S159236
                6016259
                d0ceae60-ca60-4f7a-a3c3-5f16440e1cc9
                © 2018 Zhu and Zhu. 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.

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                Original Research

                Oncology & Radiotherapy
                curcumin,mir-145,the pi3k/akt/mtor pathway,lscc
                Oncology & Radiotherapy
                curcumin, mir-145, the pi3k/akt/mtor pathway, lscc

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