2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      LINC01128 regulates the development of osteosarcoma by sponging miR‐299‐3p to mediate MMP2 expression and activating Wnt/β‐catenin signalling pathway

      research-article
      1 , 1 ,
      Journal of Cellular and Molecular Medicine
      John Wiley and Sons Inc.
      bone tumour, ceRNA, invasion, lncRNA, proliferation

      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

          Osteosarcoma (OS) is one of the most common metastatic bone cancers, which results in significant morbidity and mortality. The important role of long non‐coding RNAs (lncRNAs) in the biological processes of OS has been demonstrated through several studies. In the current study, we evaluated the role of the lncRNA, LINC01128, in OS. We analysed the expression of LINC01128 in three OS gene expression omnibus (GEO) data sets GSE21257, GSE36001 and GSE42352. The expression of LINC01128 in OS tissues and matched non‐tumour tissues obtained from 50 OS patients was detected using qRT‐PCR. The association between LINC01128 expression and overall survival of OS patients was evaluated using the Kaplan‐Meier method. The effects of LINC01128 knockdown and overexpression were evaluated through in vitro and in vivo assays. The LINC01128/miR‐299‐3p/ MMP2 axis was verified using dual‐luciferase reporter assay and qRT‐PCR assays. GEO data sets analysis revealed that the expression of LINC01128 was increased in OS. Elevated LINC01128 expression was accompanied by shorter overall survival in OS patients. Functional studies revealed that LINC01128 knockdown reduced the proliferation, migration and invasion of OS cells both in vitro and in vivo. Mechanistically, LINC01128 sponged miR‐299‐3p to increase MMP2 expression. Rescue assays determined the role of the LINC01128/miR‐299‐3p/MMP2 axis in the proliferation, migration and invasion of OS cells. Additionally, the Wnt/β‐catenin signalling pathway was activated by LINC01128 and MMP2 in OS cell lines. In summary, this study demonstrates that LINC01128 facilitates OS by functioning as a sponge of miR‐299‐3p, thus promoting MMP2 expression and activating the Wnt/β‐catenin signalling pathway.

          Related collections

          Most cited references38

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

          Osteosarcoma: Current Treatment and a Collaborative Pathway to Success.

          Osteosarcoma is the bone tumor that most commonly affects children, adolescents, and young adults. Before 1970, treatment primarily included surgical resection. However, the introduction of chemotherapy led to a dramatic improvement in prognosis for patients with localized osteosarcoma; long-term survival rates of less than 20% improved to 65% to 70% after the advent of multiagent chemotherapy regimens. Controversy concerning the ideal combination of chemotherapy agents ensued throughout the last quarter of the 20th century because of conflicting and often nonrandomized data. However, large cooperative group studies and international collaboration have demonstrated that the most effective regimens include the combination of high-dose methotrexate, doxorubicin, and cisplatin (MAP). The introduction of biologic agents such as muramyl tripeptide and the use of additional cytotoxic chemotherapy such as ifosfamide have not definitively improved the survival of patients with osteosarcoma. Collaborative efforts to increase understanding of the biology of osteosarcoma and the use of preclinical models to test novel agents will be critical to identify the path toward improving outcomes for patients. Once promising agents are identified, an international infrastructure exists for clinical trials. Herein, biologic, preclinical, and clinical trial efforts will be described along with future international collaborative strategies to improve outcomes for patients who develop this challenging tumor.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Screening and validation of lncRNAs and circRNAs as miRNA sponges.

            Intensive research in past two decades has uncovered the presence and importance of noncoding RNAs (ncRNAs), which includes microRNAs (miRs) and long ncRNAs (lncRNAs). These two classes of ncRNAs interact to a certain extent, as some lncRNAs bind to miRs to sequester them. Such lncRNAs are collectively called 'competing endogenous RNAs' or 'miRNA sponges'. In this study, we screened for lncRNAs that may act as miRNA sponges using the publicly available data sets and databases. To uncover the roles of miRNA sponges, loss-of-function experiments were conducted, which revealed the biological roles as miRNA sponges. LINC00324 is important for the cell survival by binding to miR-615-5p leading to the de-repression of its target BTG2. LOC400043 controls several biological functions via sequestering miR-28-3p and miR-96-5p, thereby changing the expressions of transcriptional regulators. Finally, we also screened for circular RNAs (circRNAs) that may function as miRNA sponges. The results were negative at least for the selected circRNAs in this study. In conclusion, miRNA sponges can be identified by applying a series of bioinformatics techniques and validated with biological experiments.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Wnt/β‐catenin/RAS signaling mediates age‐related renal fibrosis and is associated with mitochondrial dysfunction

              Abstract Renal fibrosis is the common pathological feature in a variety of chronic kidney diseases. Aging is highly associated with the progression of renal fibrosis. Among several determinants, mitochondrial dysfunction plays an important role in aging. However, the underlying mechanisms of mitochondrial dysfunction in age‐related renal fibrosis are not elucidated. Herein, we found that Wnt/β‐catenin signaling and renin–angiotensin system (RAS) activity were upregulated in aging kidneys. Concomitantly, mitochondrial mass and functions were impaired with aging. Ectopic expression of Klotho, an antagonist of endogenous Wnt/β‐catenin activity, abolished renal fibrosis in d‐galactose (d‐gal)‐induced accelerated aging mouse model and significantly protected renal mitochondrial functions by preserving mass and diminishing the production of reactive oxygen species. In an established aging mouse model, dickkopf 1, a more specific Wnt inhibitor, and the mitochondria‐targeted antioxidant mitoquinone restored mitochondrial mass and attenuated tubular senescence and renal fibrosis. In a human proximal tubular cell line (HKC‐8), ectopic expression of Wnt1 decreased biogenesis and induced dysfunction of mitochondria, and triggered cellular senescence. Moreover, d‐gal triggered the transduction of Wnt/β‐catenin signaling, which further activated angiotensin type 1 receptor (AT1), and then decreased the mitochondrial mass and increased cellular senescence in HKC‐8 cells and primary cultured renal tubular cells. These effects were inhibited by AT1 blocker of losartan. These results suggest inhibition of Wnt/β‐catenin signaling and the RAS could slow the onset of age‐related mitochondrial dysfunction and renal fibrosis. Taken together, our results indicate that Wnt/β‐catenin/RAS signaling mediates age‐related renal fibrosis and is associated with mitochondrial dysfunction.
                Bookmark

                Author and article information

                Contributors
                chenting_sjyy@126.com
                Journal
                J Cell Mol Med
                J Cell Mol Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                27 October 2020
                December 2020
                : 24
                : 24 ( doiID: 10.1111/jcmm.v24.24 )
                : 14293-14305
                Affiliations
                [ 1 ] Department of Orthopedics Shengjing Hospital of China Medical University Shenyang China
                Author notes
                [*] [* ] Correspondence

                Ting Chen, Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, Liaoning province, China.

                Email: chenting_sjyy@ 123456126.com

                Author information
                https://orcid.org/0000-0002-7736-7682
                Article
                JCMM16046
                10.1111/jcmm.16046
                7753992
                33108067
                0178cc88-2173-4313-9f45-d4fbc2fa2920
                © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 June 2020
                : 25 September 2020
                : 11 October 2020
                Page count
                Figures: 8, Tables: 1, Pages: 13, Words: 6102
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                December 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:22.12.2020

                Molecular medicine
                bone tumour,cerna,invasion,lncrna,proliferation
                Molecular medicine
                bone tumour, cerna, invasion, lncrna, proliferation

                Comments

                Comment on this article