12
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Matrine inhibits TPC-1 human thyroid cancer cells via the miR-21/PTEN/Akt pathway

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Papillary thyroid cancer (PTC) is the primary type of thyroid cancer and the most widespread endocrine malignancy. Matrine is a traditional Chinese medicine and has been demonstrated as a promising alternative drug for the treatment of TPC-1 human PTC. In the present study, the therapeutic effects and the underlying molecular mechanisms of matrine on TPC-1 cells were investigated. Treatment with matrine at the concentrations of 1, 2, 5, 10 and 20 mg/ml inhibited TPC-1 cell proliferation by up to 95.8% (for 20 mg/ml matrine). Flow cytometry indicated that treatment with 10 mg/ml matrine induced up to 61.8% apoptosis of the TPC-1 cells and the cell cycle was arrested at the G0/G1 phase following treatment with matrine (2, 5 and 10 mg/ml) for 48 h. Quantitative polymerase chain reaction indicated that the expression of microRNA (miR)-21 was downregulated and phosphatase and tensin homolog (PTEN) mRNA levels increased up to 1.66-fold following treatment with matrine, and RAC-α serine/threonine-protein kinase (Akt) mRNA levels were downregulated 0.34-fold following treatment with 5 mg/ml matrine, compared with the normal control group. Western blot analysis indicated that matrine at 2 and 5 mg/ml increased levels of the miR-21 target PTEN and decreased the levels of phosphorylated (p)Akt. Furthermore, miR-21 mimic transfection decreased the expression levels of PTEN and increased the levels of pAkt. These results suggested that the miR-21/PTEN/Akt pathway may be one of the mechanisms by which matrine induces apoptosis and cell cycle arrest in TPC-1 thyroid cancer cells. Matrine is an alternative potential drug for the treatment of thyroid cancer.

          Related collections

          Most cited references26

          • Record: found
          • Abstract: found
          • Article: not found

          MicroRNA-21 targets tumor suppressor genes in invasion and metastasis.

          MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs that target protein-coding mRNAs at the post-transcriptional level. Our previous studies suggest that mir-21 functions as an oncogene and has a role in tumorigenesis, in part through regulation of the tumor suppressor gene tropomyosin 1 (TPM1). Given that TPM1 has been implicated in cell migration, in this study we further investigated the role of mir-21 in cell invasion and tumor metastasis. We found that suppression of mir-21 in metastatic breast cancer MDA-MB-231 cells significantly reduced invasion and lung metastasis. Consistent with this, ectopic expression of TPM1 remarkably reduced cell invasion. Furthermore, we identified two additional direct mir-21 targets, programmed cell death 4 (PDCD4) and maspin, both of which have been implicated in invasion and metastasis. Like TPM1, PDCD4 and maspin also reduced invasiveness of MDA-MB-231 cells. Finally, the expression of PDCD4 and maspin inversely correlated with mir-21 expression in human breast tumor specimens, indicating the potential regulation of PDCD4 and maspin by mir-21 in these tumors. Taken together, the results suggest that, as an oncogenic miRNA, mir-21 has a role not only in tumor growth but also in invasion and tumor metastasis by targeting multiple tumor/metastasis suppressor genes. Therefore, suppression of mir-21 may provide a novel approach for the treatment of advanced cancers.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis.

            MicroRNA 21 (miR-21) is overexpressed in virtually all types of carcinomas and various types of hematological malignancies. To determine whether miR-21 promotes tumor development in vivo, we knocked out the miR-21 allele in mice. In response to the 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate mouse skin carcinogenesis protocol, miR-21-null mice showed a significant reduction in papilloma formation compared with wild-type mice. We revealed that cellular apoptosis was elevated and cell proliferation was decreased in mice deficient of miR-21 compared to wild-type animals. In addition, we found that a large number of validated or predicted miR-21 target genes were up-regulated in miR-21-null keratinocytes, which are precursor cells to skin papillomas. Specifically, up-regulation of Spry1, Pten, and Pdcd4 when miR-21 was ablated coincided with reduced phosphorylation of ERK, AKT, and JNK, three major downstream effectors of Ras activation that plays a predominant role in DMBA-initiated skin carcinogenesis. These results provide in vivo evidence that miR-21 exerts its oncogenic function through negatively regulating its target genes.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Expression of miR-21 and its targets (PTEN, PDCD4, TM1) in flat epithelial atypia of the breast in relation to ductal carcinoma in situ and invasive carcinoma

              Background Flat epithelial atypia (FEA) of the breast is characterised by a few layers of mildly atypical luminal epithelial cells. Genetic changes found in ductal carcinoma in situ (DCIS) and invasive ductal breast cancer (IDC) are also found in FEA, albeit at a lower concentration. So far, miRNA expression changes associated with invasive breast cancer, like miR-21, have not been studied in FEA. Methods We performed miRNA in-situ hybridization (ISH) on 15 cases with simultaneous presence of normal breast tissue, FEA and/or DCIS and 17 additional cases with IDC. Expression of the miR-21 targets PDCD4, TM1 and PTEN was investigated by immunohistochemistry. Results Two out of fifteen cases showed positive staining for miR-21 in normal breast ductal epithelium, seven out of fifteen cases were positive in the FEA component and nine out of twelve cases were positive in the DCIS component. A positive staining of miR-21 was observed in 15 of 17 IDC cases. In 12 cases all three components were present in one tissue block and an increase of miR-21 from normal breast to FEA and to DCIS was observed in five cases. In three cases the FEA component was negative, whereas the DCIS component was positive for miR-21. In three other cases, normal, FEA and DCIS components were negative for miR-21 and in the last case all three components were positive. Overall we observed a gradual increase in percentage of miR-21 positive cases from normal, to FEA, DCIS and IDC. Immunohistochemical staining for PTEN revealed no obvious changes in staining intensities in normal, FEA, DCIS and IDC. Cytoplasmic staining of PDCD4 increased from normal to IDC, whereas, the nuclear staining decreased. TM1 staining decreased from positive in normal breast to negative in most DCIS and IDC cases. In FEA, the staining pattern for TM1 was similar to normal breast tissue. Conclusion Upregulation of miR-21 from normal ductal epithelial cells of the breast to FEA, DCIS and IDC parallels morphologically defined carcinogenesis. No clear relation was observed between the staining pattern of miR-21 and its previously reported target genes.
                Bookmark

                Author and article information

                Journal
                Oncol Lett
                Oncol Lett
                OL
                Oncology Letters
                D.A. Spandidos
                1792-1074
                1792-1082
                September 2018
                21 June 2018
                21 June 2018
                : 16
                : 3
                : 2965-2970
                Affiliations
                [1 ]Department of Thyroid Surgery, Jilin University China-Japan Union Hospital, Changchun, Jilin 130033, P.R. China
                [2 ]Department of Hand Surgery, Jilin University China-Japan Union Hospital, Changchun, Jilin 130033, P.R. China
                Author notes
                Correspondence to: Dr Shusen Cui, Department of Hand Surgery, Jilin University China-Japan Union Hospital, 126 Xiantai Street, Changchun, Jilin 130033, P.R. China, E-mail: cuisjlu@ 123456sina.com
                Article
                OL-0-0-9006
                10.3892/ol.2018.9006
                6096072
                65559396-c7d7-4f36-8d41-c1079768c012
                Copyright: © Zhao 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
                : 05 February 2018
                : 31 May 2018
                Categories
                Articles

                Oncology & Radiotherapy
                matrine,mir-21,thyroid cancer,apoptosis,cell cycle arrest,phosphatase and tensin homolog,akt

                Comments

                Comment on this article