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      miR-329 inhibits papillary thyroid cancer progression via direct targeting WNT1

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          Abstract

          Dysregulated microRNA-329 (miR-329) serves an important role in the progression of certain types of tumor. However, the exact function and mechanisms of miR-329 in papillary thyroid cancer (PTC) remain unknown. The present study investigated the function and mechanisms of miR-329 in regulating PTC cell progression. The results revealed that the expression of miR-329 was significantly downregulated in PTC tissues and cell lines compared with adjacent normal tissues and a human immortalized follicular cell line. miR-329 mimics notably decreased PTC cell proliferation, colony formation and WNT1 expression in vitro, as well as suppressing PTC tumor growth in vivo. In addition, luciferase assays determined that miR-329 was able to directly bind with the 3′untranslated region of WNT1. Furthermore, short interfering RNA-WNT1-induced downregulation of WNT1, which demonstrated similar effects to miR-329 overexpression. WNT1 overexpression rescued the tumor suppressive effects of miR-329 in PTC cells. The present study provided new insights into the role of miR-329 in PTC progression and suggests the potential application of miR-329 as a therapy for PTC.

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          Mechanisms of miRNA-Mediated Gene Regulation from Common Downregulation to mRNA-Specific Upregulation

          Discovered in 1993, micoRNAs (miRNAs) are now recognized as one of the major regulatory gene families in eukaryotes. To date, 24521 microRNAs have been discovered and there are certainly more to come. It was primarily acknowledged that miRNAs result in gene expression repression at both the level of mRNA stability by conducting mRNA degradation and the level of translation (at initiation and after initiation) by inhibiting protein translation or degrading the polypeptides through binding complementarily to 3′UTR of the target mRNAs. Nevertheless, some studies revealed that miRNAs have the capability of activating gene expression directly or indirectly in respond to different cell types and conditions and in the presence of distinct cofactors. This reversibility in their posttranslational gene regulatory natures enables the bearing cells to rapidly response to different cell conditions and consequently block unnecessary energy wastage or maintain the cell state. This paper provides an overview of the current understandings of the miRNA characteristics including their genes and biogenesis, as well as their mediated downregulation. We also review up-to-date knowledge of miRNA-mediated gene upregulation through highlighting some notable examples and discuss the emerging concepts of their associations with other posttranscriptional gene regulation processes.
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            Thyroid cancer cell lines: an overview

            Human thyroid cancer cell lines are the most used models for thyroid cancer studies. They must be used with detailed knowledge of their characteristics. These in vitro cell lines originate from differentiated and dedifferentiated in vivo human thyroid tumors. However, it has been shown that mRNA expression profiles of these cell lines were closer to dedifferentiated in vivo thyroid tumors (anaplastic thyroid carcinoma, ATC) than to differentiated ones. Here an overview of the knowledge of these models was made. The mutational status of six human thyroid cancer cell lines (WRO, FTC133, BCPAP, TPC1, K1, and 8505C) was in line with previously reported findings for 10 genes frequently mutated in thyroid cancer. However, the presence of a BRAF mutation (T1799A: V600E) in WRO questions the use of this cell line as a model for follicular thyroid carcinoma (FTC). Next, to investigate the biological meaning of the modulated mRNAs in these cells, a pathway analysis on previously obtained mRNA profiles was performed on five cell lines. In five cell lines, the MHC class II pathway was down-regulated and in four of them, ribosome biosynthesis and translation pathways were up-regulated. mRNA expression profiles of the cell lines were also compared to those of the different types of thyroid cancers. Three datasets originating from different microarray platforms and derived from distinct laboratories were used. This meta-analysis showed a significant higher correlation between the profiles of the thyroid cancer cell lines and ATC, than to differentiated thyroid tumors (i.e., PTC or FTC) specifically for DNA replication. This already observed higher correlation was obtained here with an increased number of in vivo tumors and using different platforms. In summary, this would suggest that some papillary thyroid carcinoma or follicular thyroid carcinoma (PTC or FTC) cell lines (i.e., TPC-1) might have partially lost their original DNA synthesis/replication regulation mechanisms during their in vitro cell adaptation/evolution.
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              Prognostic Significance of Wnt-1, β-catenin and E-cadherin Expression in Advanced Colorectal Carcinoma

              Wnt/β-catenin pathway plays an important role in initiation and progression of colorectal oncogenesis. The aim of this study was to determine expression and localization of E-cadherin, β-catenin and Wnt-1 proteins in colorectal tumors. Expression of β-catenin, E-cadherin and Wnt-1 was determined by immunohistochemistry on advanced colorectal cancers. Abnormal expression of E-cadherin, β-catenin, Wnt-1 was observed. Additionally, we revealed correlations between levels of studied proteins and histoclinical data. In multivariate analysis nuclear β-catenin, higher carcinoembryonic antigen serum level before treatment, female sex and tumor localized in colon or rectum were independent unfavorable prognostic factors. These findings support the hypothesis that Wnt/β-catenin pathway plays an important role in advanced colorectal carcinoma.
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                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                September 2018
                06 July 2018
                06 July 2018
                : 16
                : 3
                : 3561-3568
                Affiliations
                [1 ]Department of Oncology, Linyi Central Hospital, Linyi, Shandong 276400, P.R. China
                [2 ]Department of Breast Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
                Author notes
                Correspondence to: Dr Deliang Ma, Department of Oncology, Linyi Central Hospital, 17 Jian Kang Road, Yishui, Linyi, Shandong 276400, P.R. China, E-mail: madeliang2018@ 123456163.com
                Article
                OL-0-0-9102
                10.3892/ol.2018.9102
                6096240
                a57360b1-22a8-48fe-87b4-e4fbad16bf24
                Copyright: © Wu 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
                : 13 January 2018
                : 29 June 2018
                Categories
                Articles

                Oncology & Radiotherapy
                papillary thyroid cancer,migration and invasion,proliferation,microrna-329,wnt1

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