Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2015 Volume 12 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells

  • Authors:
    • Jin‑Hang Wang
    • Wen‑Wen Zhou
    • Shi‑Tong Cheng
    • Bo‑Xin Liu
    • Fu‑Rong Liu
    • Jian‑Qing Song
  • View Affiliations / Copyright

    Affiliations: Department of Laboratory Medicine, The First Hospital Affiliated to China Medical University Clinical Laboratory, Shenyang, Liaoning 110000, P.R. China, Department of Cell Biology, China Medical University, Key Laboratory of Medical Cell Biology, Ministry of Public Health, Shenyang, Liaoning 110000, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
  • Pages: 1810-1816
    |
    Published online on: March 30, 2015
       https://doi.org/10.3892/mmr.2015.3567
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The aim of the present study was to assess the effects of sprouty homolog 2 (SPRY2) gene regulation by miR-21 on the occurrence, development and tumor metastasis in multiple myeloma (MM). The miR‑21 expression lentiviral vector (LV)‑anti‑miR‑21 and a liposome transfection method were used to screen MM cell lines with stable silent SPRY2. Real‑time quantitative polymerase chain reaction (PCR) and western blot analyses were used to detect SPRY2 expression and miR‑21 protein expression levels. An MTT assay was used to assess cell proliferation. Flow cytometry was used for analysis of cell cycle. A scratch test/wound healing assay was used to detect the cell migration ability. A Transwell assay was used to detect the cell invasion ability. Real‑time quantitative PCR and western blot analysis showed that in the MM cell lines with high endogenous miR‑21 expression (RPMI8226 and KM3), SPRY2 expression was significantly lower. Conversely, in the U266 cell line with low endogenous miR‑21 expression, SPRY2 expression was significantly higher, and the gray values of miR‑21 and SPRY2 protein in the respective cell lines showed statistically significant differences (P<0.01). Following transfection of U266 cells, the expression of miR‑21 in the U266/LV‑anti‑miR21 lentiviral multiplicity of infection (MOI) 20 group and ‑MOI 40 group decreased significantly compared with that in the untransfected U266 group (P<0.05). SPRY2 protein expression in U266 cells transfected with miR‑21 mimics was significantly reduced compared with that in the non‑transfected (untreated) group and the negative control‑transfected group (P<0.01). An MTT assay showed that compared with the non‑transfected and negative control groups, the cell growth rate as well as the proliferation rate were significantly decreased in the transfection group 48, 72 and 96 h after transfection (P<0.01). Flow cytometric analysis showed that 48 and 72 h after transfection of U266 cells with miR‑21 mimics, the apoptotic rates were (24.7±1.97 and 38.6±1.56%) in the U266 group, (27.3±1.72 and 37.3±1.59%) in the siRNA group and (12.7±1.27 and 22.1±1.63%) in the U266/miR‑21 group. Compared with the two control groups, the apoptotic rate in the U266/miR‑21 group was significantly decreased and the G0/G1 phase cell population was significantly reduced (P<0.05). Scratch experiments showed that the cell migration ability was significantly reduced in the transfection group 24 and 48 h after transfection (P<0.05). A Transwell invasion assay confirmed that the number of U266 cells which migrated through a Matrigel‑covered polyphosphate membrane significantly decreased in the transfection group 24 and 48 h after transfection. The cell‑penetrating ability was also significantly decreased (P<0.05). In conclusion, the downregulation of SPRY2 gene expression mediated by miR-21 promotes the proliferation and invasion of MM cells in vitro, suggesting that miR-21 may be a novel potential molecular therapeutic target in the treatment of MM.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

View References

1 

Hatzimichael E, Dasoula A, Benetatos L, Syed N, Dranitsaris G, Crook T and Bourantas K: Study of specific genetic and epigenetic variables in multiple myeloma. Leuk Lymphoma. 51:2270–2274. 2010. View Article : Google Scholar : PubMed/NCBI

2 

Anderson KC: Multiple myeloma: How far have we come? Mayo Clin Proc. 78:15–17. 2003. View Article : Google Scholar : PubMed/NCBI

3 

Pichiorri F, Suh SS, Ladetto M, Kuehl M, Palumbo T, Drandi D, Taccioli C, Zanesi N, Alder H, Hagan JP, Munker R, Volinia S, Boccadoro M, Garzon R, Palumbo A, Aqeilan RI and Croce CM: MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci USA. 105:12885–12890. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Murphy T, Hori S, Sewell J and Gnanapragasam VJ: Expression and functional role of negative signalling regulators in tumour development and progression. Int J Cancer. 127:2491–2499. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Edwin F, Anderson K, Ying C and Patel TB: Intermolecular interactions of Sprouty proteins and their implications in development and disease. Mol Pharmacol. 76:679–691. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Feng YH, Wu CL, Shiau AL, Lee JC, Chang JG, Lu PJ, Tung CL, Feng LY, Huang WT and Tsao CJ: MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells. Int J Mol Med. 29:920–926. 2012.PubMed/NCBI

7 

Lao DH, Chandramouli S, Yusoff P, Fong CW, Saw TY, Tai LP, Yu CY, Leong HF and Guy GR: A Src homology 3-binding sequence on the C terminus of Sprouty2 is necessary for inhibition of the Ras/ERK pathway downstream of fibroblast growth factor receptor stimulation. J Biol Chem. 281:29993–30000. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Sayed D, Rane S, Lypowy J, He M, Chen IY, Vashistha H, Yan L, Malhotra A, Vatner D and Abdellatif M: MicroRNA-21 targets Sprouty2 and promotes cellular out growths. Mol Biol Cell. 19:3272–3282. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, Lao KQ, Livak KJ and Guegler KJ: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI

10 

Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C (T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar

11 

Moriyama T, Ohuchida K, Mizumoto K, et al: MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance. Mol Cancer Ther. 8:1067–1074. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Neri A, Giordano A, Munshi NC, Anderson KC, Tagliaferri P and Tassone P: Targeting miR-21 inhibits in vitro and in vivo multiple myeloma cell growth. Clin Cancer Res. 19:209–106. 2013.

13 

Löffler D, Brocke-Heidrich K, Pfeifer G, Stocsits C, Hackermüller J, Kretzschmar AK, Burger R, Gramatzki M, Blumert C, Bauer K, Cvi jic H, Ullmann AK, Stadler PF and Horn F: Interleukin-6 dependent survival of multiple myeloma cells involves the Stat3-mediated induction of microRNA-21 through a highly conserved enhancer. Blood. 110:1330–1333. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Hu HY, Li KP, Wang XJ, Liu Y, Lu ZG, Dong RH, Guo HB and Zhang MX: Set9, NF-kappaB and microRNA-21 mediate berberine-induced apoptosis of human multiple myeloma cells. Acta Pharmacol Sin. 34:157–166. 2013. View Article : Google Scholar

15 

Liu C, Yu J, Yu S, Lavker RM, Cai L, Liu W, Yang K, He X and Chen S: MicroRNA-21 acts as an oncomir through multiple targets in human hepatocellular carcinoma. J Hepatol. 53:98–107. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Xu J, Wu C, Che X, Wang L, Yu D, Zhang T, Huang L, Li H, Tan W, Wang C and Lin D: Circulating microRNAs, miR-21, miR-122 and miR-223, in patients with hepatocellular carcinoma or chronic hepatitis. Mol Carcinog. 50:136–142. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Pichiorri F, Suh SS, Ladetto M, Kuehl M, Palumbo T, Drandi D, Taccioli C, Zanesi N, Alder H, Hagan JP, Munker R, Volinia S, Boccadoro M, Garzon R, Palumbo A, Aqeilan RI and Croce CM: MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis. Proc Natl Acad Sci USA. 105:12885–12890. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Cabrita MA and Christofori G: Sprouty proteins, masterminds of receptor tyrosine kinase signaling. Angiogenesis. 11:53–62. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Lito P, Mets BD, Kleff S, O’Reilly S, Maher VM and McCormick JJ: Evidence that sprouty 2 is necessary for sarcoma formation by H-Ras oncogene-transformed human fibroblasts. J Biol Chem. 283:2002–2009. 2008. View Article : Google Scholar

20 

Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S and Allgayer H: MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene. 27:2128–2136. 2008. View Article : Google Scholar

21 

Yedjou CG and Tchounwou PB: In-vitor cytotoxic and genotoxic effects of arsenic trioxide on human leukemia (HL-60) cells using the MTT and alkaline single cell gelelectrophoresis (Comet) assays. Mol Cell Biochem. 301:123–130. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Feng YH, Wu CL, Tsao CJ, Chang JG, Lu PJ, Yeh KT, Uen YH, Lee JC and Shiau AL: Deregulated expression of sprouty2 and microRNA-21 in human colon cancer: Correlation with the clinical stage of the disease. Cancer Biol Ther. 11:111–121. 2011. View Article : Google Scholar

23 

Wang X, Li C, Ju S, Wang Y, Wang H and Zhong R: Myeloma cell adhesion to bone marrow stromal cells confers drug resistance by microRNA-21 up-regulation. Leuk Lymphoma. 52:1991–1998. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Xiong Q, Zhong Q, Zhang J, Yang M, Li C, Zheng P, Bi LJ and Ge F: Identification of novel miR-21 target proteins in multiplemyeloma cells by quantitative proteomics. J Proteome Res. 11:2078–2090. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Shah AA, Leidinger P, Blin N and Meese E: miRNA: small molecules as potential novel biomarkers in cancer. Curr Med Chem. 17:4427–4432. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang JH, Zhou WW, Cheng ST, Liu BX, Liu FR and Song JQ: Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells. Mol Med Rep 12: 1810-1816, 2015.
APA
Wang, J., Zhou, W., Cheng, S., Liu, B., Liu, F., & Song, J. (2015). Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells. Molecular Medicine Reports, 12, 1810-1816. https://doi.org/10.3892/mmr.2015.3567
MLA
Wang, J., Zhou, W., Cheng, S., Liu, B., Liu, F., Song, J."Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells". Molecular Medicine Reports 12.2 (2015): 1810-1816.
Chicago
Wang, J., Zhou, W., Cheng, S., Liu, B., Liu, F., Song, J."Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells". Molecular Medicine Reports 12, no. 2 (2015): 1810-1816. https://doi.org/10.3892/mmr.2015.3567
Copy and paste a formatted citation
x
Spandidos Publications style
Wang JH, Zhou WW, Cheng ST, Liu BX, Liu FR and Song JQ: Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells. Mol Med Rep 12: 1810-1816, 2015.
APA
Wang, J., Zhou, W., Cheng, S., Liu, B., Liu, F., & Song, J. (2015). Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells. Molecular Medicine Reports, 12, 1810-1816. https://doi.org/10.3892/mmr.2015.3567
MLA
Wang, J., Zhou, W., Cheng, S., Liu, B., Liu, F., Song, J."Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells". Molecular Medicine Reports 12.2 (2015): 1810-1816.
Chicago
Wang, J., Zhou, W., Cheng, S., Liu, B., Liu, F., Song, J."Downregulation of Sprouty homolog 2 by microRNA-21 inhibits proliferation, metastasis and invasion, however promotes the apoptosis of multiple myeloma cells". Molecular Medicine Reports 12, no. 2 (2015): 1810-1816. https://doi.org/10.3892/mmr.2015.3567
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team