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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October-2018 Volume 16 Issue 4

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
October-2018 Volume 16 Issue 4

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

Identification of a novel splice variant of the human musashi‑1 gene

  • Authors:
    • Lin Ma
    • Yating Shan
    • Heliang Ma
    • Ihab Elshoura
    • Muhammad Nafees
    • Kaiyong Yang
    • Wu Yin
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Pharmaceutical Biotechnology, College of Life Sciences, Nanjing University, Nanjing, Jiangsu 210046, P.R. China, Department of Radiology, Jinan Central Hospital, Jinan, Shandong 250013, P.R. China, State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 210046, P.R. China
  • Pages: 5441-5448
    |
    Published online on: August 13, 2018
       https://doi.org/10.3892/ol.2018.9300
  • 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

Musashi‑1 (Msi1) is an evolutionarily conserved RNA‑binding protein that has been reported to be the key regulator in malignancies and with involvement in cancer stemness. In the present study, a novel Msi1 transcript variant generated by alternative splicing was identified and termed Msi1 variant 2. This variant was observed to be ubiquitously expressed in cancerous and non‑cancerous cells compared with its wild‑type variant, which is preferentially expressed in cancer cells. Notably, the expression levels of Msi1 variant 2 were inversely associated with the protein expression levels of Msi1 in various cancer cells. This naturally truncated variant contains 899 nucleotides and a skipping event of exons 3 and 4, which leads to the emergence of a premature TGA stop codon in exon 5. The present results also demonstrated that hypoxia increased the resistance of H460 cells to cisplatin by suppressing the exon 3 and 4 skipping event of Msi1. In summary, the present study identified a novel splice variant of Msi1 lacking two complete RNA recognition motifs, and revealed the role of exon 3 and 4 skipping of Msi1 pre‑mRNA in regulating cisplatin resistance under hypoxia. These observations indicate that targeting Msi1 alternative splicing could represent a valuable strategy to repress Msi1 signaling in tumors overexpressing this RNA‑binding protein.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Rosenthal N: Regulation of gene expression. N Engl J Med. 331:931–933. 1994. View Article : Google Scholar : PubMed/NCBI

2 

Krijger PH and De Laat W: Regulation of disease-associated gene expression in the 3D genome. Nat Rev Mol Cell Biol. 17:771–782. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Lopez AJ: Alternative splicing of pre-mRNA: Developmental consequences and mechanisms of regulation. Annu Rev Genet. 32:279–305. 1998. View Article : Google Scholar : PubMed/NCBI

4 

Hong H, Braunschweig U, Gonatopoulos-Pournatzis T, Weatheritt RJ, Hirsch CL, Ha KCH, Radovani E, Nabeel-Shah S, Sterne-Weiler T, Wang J, et al: Multilayered control of alternative splicing regulatory networks by transcription factors. Mol Cell. 65:539–553.e7. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Talavera D, Orozco M and de la Cruz X: Alternative splicing of transcription factors' genes: Beyond the increase of proteome diversity. Comp Funct Genomics. 2009:Article ID 9058942009. View Article : Google Scholar

6 

Singh B and Eyras E: The role of alternative splicing in cancer. Transcription. 8:91–98. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Kim YJ and Kim HS: Alternative splicing and its impact as a cancer diagnostic marker. Genomics Inform. 10:74–80, 2017. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Hofstetter G, Berger AH, Slade N, Zorić A, Holzer B, Schuster E, Schuster E, Mobus VJ, Reimer D, Daxenbichler G, et al: Alternative splicing of p53 and p73: The novel p53 splice variant p53delta is an independent prognostic marker in ovarian cancer. Oncogene. 29:1997–2004. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Hironori K, Takao I, Hiroaki I, Masafumi T, Ken M and Hideyuki O: Neural RNA-binding protein Musashi1 inhibits translation initiation by competing with eIF4G for PABP. J Cell Biol. 181:639–653. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Imai T, Tokunaga A, Yoshida T, Hashimoto M, Mikoshiba K, Weinmaster G, Nakafuku M and Okano H: The neural RNA-binding protein Musashi1 translationally regulates mammalian numb gene expression by interacting with its mRNA. Mol Cell Biol. 21:3888–3900. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Chen HY, Lin LT, Wang ML, Lee SH, Tsai ML, Tsai CC, Liu WH, Chen TC, Yang YP, Lee YY, et al: Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma. Oncotarget. 7:42485–42501. 2016.PubMed/NCBI

12 

Rezza A, Skah S, Roche C, Nadjar J, Samarut J and Plateroti M: The overexpression of the putative gut stem cell marker Musashi-1 induces tumorigenesis through Wnt and Notch activation. J Cell Sci. 123:3256–3265. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Toda M, Iizuka Y, Yu W, Imai T, Ikeda E, Yoshida K, Kawase T, Kawakami Y, Okano H and Uyemura K: Expression of the neural RNA-binding protein Musashi1 in human gliomas. Glia. 34:1–7. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Nishimoto Y and Okano H: New insight into cancer therapeutics: Induction of differentiation by regulating the Musashi/Numb/Notch pathway. Cell Res. 20:1083–1085. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Wang XY, Yu H, Linnoila RI, Li L, Li D, Mo B, Okano H, Penalva LO and Glazer RI: Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer. Oncotarget. 4:739–750. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Shi H, Pu J, Zhou XL, Ning YY and Bai C: Silencing long non-coding RNA ROR improves sensitivity of non-small-cell lung cancer to cisplatin resistance by inhibiting PI3K/Akt/mTOR signaling pathway. Tumour Biol. 39:2017. View Article : Google Scholar

17 

Li X, You M, Liu YJ, Ma L, Jin PP, Zhou R, Zhang ZX, Hua B, Ji XJ, Cheng XY, et al: Reversal of the apoptotic resistance of non-small-cell lung carcinoma towards TRAIL by natural product toosendanin. Sci Rep. 7:427482017. View Article : Google Scholar : PubMed/NCBI

18 

Cui R, Zhang H, Guo X, Cui Q, Wang J and Dai J: Proteomic analysis of cell proliferation in a human hepatic cell line (HL-7702) induced by perfluorooctane sulfonate using iTRAQ. J Hazard Mater. 299:361–370. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Wan C, Gong C, Ji L, Liu X, Wang Y, Wang L, Shao M, Yang L, Fan S, Xiao Y, et al: NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma. Mol Cell Biochem. 410:25–35. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Muz B, de la Puente P, Azab F and Azab AK: The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl). 3:83–92. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Okano H, Kawahara H, Toriya M, Nakao K, Shibata S and Imai T: Function of RNA-binding protein Musashi-1 in stem cells. Exp Cell Res. 306:349–356. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Chiou GY, Yang TW, Huang CC, Tang CY, Yen JY, Tsai MC, Chen HY, Fadhilah N, Lin CC and Jong YJ: Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells. Sci Rep. 7:21722017. View Article : Google Scholar : PubMed/NCBI

23 

Zhao W, Li Y and Zhang X: Stemness-related markers in cancer. Cancer Transl Med. 3:87–95. 2017. View Article : Google Scholar : PubMed/NCBI

24 

Battelli C, Nikopoulos GN, Mitchell JG and Verdi JM: The RNA-binding protein Musashi-1 regulates neural development through the translational repression of p21WAF-1. Mol Cell Neurosci. 31:85–96. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Hong J, Liu Z, Zhu H, Zhang X, Liang Y, Yao S, Wang F, Xie X, Zhang B, Tan T, et al: The tumor suppressive role of NUMB isoform 1 in esophageal squamous cell carcinoma. Oncotarget. 5:5602–5614. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Kang Y, Ding M, Tian G, Guo H, Wan Y, Yao Z, Li B and Lin D: Overexpression of Numb suppresses tumor cell growth and enhances sensitivity to cisplatin in epithelioid malignant pleural mesothelioma. Oncol Rep. 30:313–319. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Chilosi M, Doglioni C, Magalini A, Inghirami G, Krampera M, Nadali G, Rahal D, Pedron S, Benedetti A, Scardoni M, et al: p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: A potential marker of p53 tumor-suppressor gene function. Blood. 88:4012–4020. 1996.PubMed/NCBI

28 

Wolfe AR, Ernlund A, Mcguinness W, Lehmann C, Carl K, Balmaceda N and Neufeld KL: Suppression of intestinal tumorigenesis in Apc mutant mice upon Musashi-1 deletion. J Cell Sci. 130:805–813. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Maris C, Dominguez C and Allain FH: The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression. FEBS J. 272:2118–2131. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Pastore C, Topalidou I, Forouhar F, Yan AC, Levy M and Hunt JF: Crystal structure and RNA binding properties of the RNA recognition motif (RRM) and AlkB domains in human AlkB homolog 8 (ABH8), an enzyme catalyzing tRNA hypermodification. J Biol Chem. 287:2130–2143. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Giampietri C, Petrungaro S, Conti S, Facchiano A, Filippini A and Ziparo E: Cancer microenvironment and endoplasmic reticulum stress response. Mediators Inflamm. 2015:4172812015. View Article : Google Scholar : PubMed/NCBI

32 

Urra H, Dufey E, Avril T, Chevet E and Hetz C: Endoplasmic reticulum stress and the hallmarks of cancer. Trends Cancer. 2:252–262. 2016. View Article : Google Scholar : PubMed/NCBI

33 

Sullivan R, Paré GC, Frederiksen LJ, Semenza GL and Graham CH: Hypoxia-induced resistance to anticancer drugs is associated with decreased senescence and requires hypoxia-inducible factor-1 activity. Mol Cancer Ther. 7:1961–1973. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Schnitzer SE, Weigert A, Zhou J and Brüne B: Hypoxia enhances sphingosine kinase 2 activity and provokes sphingosine-1-phosphate-mediated chemoresistance in A549 lung cancer cells. Mol Cancer Res. 7:393–401. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Lan L, Appelman C, Smith AR, Yu J, Larsen S, Marquez RT, Liu H, Wu X, Gao P, Roy A, et al: Natural product (−)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1. Mol Oncol. 9:1406–1420. 2015. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma L, Shan Y, Ma H, Elshoura I, Nafees M, Yang K and Yin W: Identification of a novel splice variant of the human musashi‑1 gene. Oncol Lett 16: 5441-5448, 2018.
APA
Ma, L., Shan, Y., Ma, H., Elshoura, I., Nafees, M., Yang, K., & Yin, W. (2018). Identification of a novel splice variant of the human musashi‑1 gene. Oncology Letters, 16, 5441-5448. https://doi.org/10.3892/ol.2018.9300
MLA
Ma, L., Shan, Y., Ma, H., Elshoura, I., Nafees, M., Yang, K., Yin, W."Identification of a novel splice variant of the human musashi‑1 gene". Oncology Letters 16.4 (2018): 5441-5448.
Chicago
Ma, L., Shan, Y., Ma, H., Elshoura, I., Nafees, M., Yang, K., Yin, W."Identification of a novel splice variant of the human musashi‑1 gene". Oncology Letters 16, no. 4 (2018): 5441-5448. https://doi.org/10.3892/ol.2018.9300
Copy and paste a formatted citation
x
Spandidos Publications style
Ma L, Shan Y, Ma H, Elshoura I, Nafees M, Yang K and Yin W: Identification of a novel splice variant of the human musashi‑1 gene. Oncol Lett 16: 5441-5448, 2018.
APA
Ma, L., Shan, Y., Ma, H., Elshoura, I., Nafees, M., Yang, K., & Yin, W. (2018). Identification of a novel splice variant of the human musashi‑1 gene. Oncology Letters, 16, 5441-5448. https://doi.org/10.3892/ol.2018.9300
MLA
Ma, L., Shan, Y., Ma, H., Elshoura, I., Nafees, M., Yang, K., Yin, W."Identification of a novel splice variant of the human musashi‑1 gene". Oncology Letters 16.4 (2018): 5441-5448.
Chicago
Ma, L., Shan, Y., Ma, H., Elshoura, I., Nafees, M., Yang, K., Yin, W."Identification of a novel splice variant of the human musashi‑1 gene". Oncology Letters 16, no. 4 (2018): 5441-5448. https://doi.org/10.3892/ol.2018.9300
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