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Article Open Access

ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT

  • Authors:
    • Qingsong Zuo
    • Jie Wang
    • Chao Chen
    • Yong Zhang
    • Dian‑Xu Feng
    • Ronghua Zhao
    • Teng Chen
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
    Copyright: © Zuo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3751-3759
    |
    Published online on: August 8, 2018
       https://doi.org/10.3892/mmr.2018.9363
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Abstract

Achaete‑scute homolog 2 (ASCL2), a basic helix‑loop‑helix transcription factor, serves an essential role in the maintenance of adult intestinal stem cells and the growth of gastric cancer (GC). However, the function of ASCL2 in the metastasis of GC is poorly understood. The present study aimed to evaluate the effect of ASCL2 expression on gastric tumor metastasis. ASCL2 protein expression was detected in 32 cases of gastric metastasis and its relevant primary tumors using western blotting and immunohistochemistry. The data suggested that the expression of ASCL2 was highest in metastatic tumors, among adjacent normal tissues, primary gastric tumors and gastric metastatic tumors. Furthermore, ASCL2‑overexpressing GC cell lines MKN1‑ASCL2 and SNU16‑ASCL2 were established. An in vitro assay suggested that microRNA 223 (miR223) expression was downregulated following ASCL2 overexpression, and that the expression of the epithelium‑associated protein E‑cadherin was significantly decreased, while a series of mesenchyme‑associated proteins, including zinc finger E‑box‑binding homeobox 1 (Zeb‑1), twist‑related protein 1, integrin, vimentin, 72 kDa type IV collagenase and matrix metalloproteinase‑9 were upregulated in ASCL2‑overexpressing cells. Overexpression of miR223 attenuated the epithelial‑mesenchymal transition (EMT)‑promoting effect induced by ASCL2 expression. In addition, the results of the chromatin immunoprecipitation and luciferase reporter gene assays indicated that ASCL2 was able to interact with the promoter of pre‑miR223, and to inhibit the maturation of miR223, which may interact with the 3' untranslated region of Zeb‑1 and inhibit EMT in tumor cells. The results of the present study demonstrated that ASCL2 was able to downregulate the expression level of miR223, contribute to EMT and promote gastric tumor metastasis, which indicated that ASCL2 may serve as a therapeutic target in the treatment of GC.
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Copy and paste a formatted citation
Spandidos Publications style
Zuo Q, Wang J, Chen C, Zhang Y, Feng DX, Zhao R and Chen T: ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT. Mol Med Rep 18: 3751-3759, 2018.
APA
Zuo, Q., Wang, J., Chen, C., Zhang, Y., Feng, D., Zhao, R., & Chen, T. (2018). ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT. Molecular Medicine Reports, 18, 3751-3759. https://doi.org/10.3892/mmr.2018.9363
MLA
Zuo, Q., Wang, J., Chen, C., Zhang, Y., Feng, D., Zhao, R., Chen, T."ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT". Molecular Medicine Reports 18.4 (2018): 3751-3759.
Chicago
Zuo, Q., Wang, J., Chen, C., Zhang, Y., Feng, D., Zhao, R., Chen, T."ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT". Molecular Medicine Reports 18, no. 4 (2018): 3751-3759. https://doi.org/10.3892/mmr.2018.9363
Copy and paste a formatted citation
x
Spandidos Publications style
Zuo Q, Wang J, Chen C, Zhang Y, Feng DX, Zhao R and Chen T: ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT. Mol Med Rep 18: 3751-3759, 2018.
APA
Zuo, Q., Wang, J., Chen, C., Zhang, Y., Feng, D., Zhao, R., & Chen, T. (2018). ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT. Molecular Medicine Reports, 18, 3751-3759. https://doi.org/10.3892/mmr.2018.9363
MLA
Zuo, Q., Wang, J., Chen, C., Zhang, Y., Feng, D., Zhao, R., Chen, T."ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT". Molecular Medicine Reports 18.4 (2018): 3751-3759.
Chicago
Zuo, Q., Wang, J., Chen, C., Zhang, Y., Feng, D., Zhao, R., Chen, T."ASCL2 expression contributes to gastric tumor migration and invasion by downregulating miR223 and inducing EMT". Molecular Medicine Reports 18, no. 4 (2018): 3751-3759. https://doi.org/10.3892/mmr.2018.9363
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