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Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells

  • Authors:
    • Xiaojun Yang
    • Hui Cai
    • Yuhe Liang
    • Lin Chen
    • Xiangdong Wang
    • Ruohuang Si
    • Kunpeng Qu
    • Zebin Jiang
    • Bingqiang Ma
    • Changfeng Miao
    • Jing Li
    • Bin Wang
    • Peng Gao

  • View Affiliations

  • Published online on: January 28, 2015     https://doi.org/10.3892/or.2015.3757
  • Pages: 1723-1730
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
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Abstract

Chemotherapy is one of the few effective choices for patients with advanced or recurrent gastric cancer (GC). However, the development of mutidrug resistance (MDR) to cancer chemotherapy is a major obstacle to the effective treatment of advanced GC. Additionally, the mechanism of MDR remains to be determined. In the present study, we tested IC50 of cisplating (DDP), vincristine (VCR) and 5-fluorouracil (5-FU) in SGC7901, SGC7901/DDP and SGC7901/VCR gastric cancer cells using an MTT assay. The expression of let-7b and c-Myc in these cells was detected by qPCR and western blot analysis. The relationship between let-7b and c-Myc was explored using a luciferase reporter assay. Transfection of let-7b mimic or inhibitor was used to confirm the effect of let-7b on drug sensitivity in chemotherapy via the regulation of c-Myc expression. We found that the expression of let-7b was lower in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells than that in chemotherapy-sensitive SGC7901 cells. By contrast, the expression of c-Myc was higher in SGC7901/DDP and SGC7901/VCR cells than that in SGC7901 cells. Furthermore, we confirmed that let-7b suppresses c-Myc gene expression at the mRNA and protein levels in a sequence-specific manner, while transfection of let-7b mimic increases drug sensitivity in chemotherapy-resistant SGC7901/DDP and SGC7901/VCR cells by targeting downregulation of c-Myc. In SGC7901 drug-sensitive cells, however, the sensitivity of chemotherapy was significantly decreased following let-7b inhibitor transfection. The present study results demonstrated that let-7b increases drug sensitivity in chemotherapy‑resistant SGC7901/DDP and SGC7901/VCR gastric cancer cells by targeting the downregulation of c-Myc and that, let-7b mimic reverses MDR by promoting cancer stem cell differentiation controlled by double-negative autoregulatory loops (Lin28/let-7 and Myc/let-7) and a double-positive autoregulatory loop (Lin28/Lin28B/Myc) existing in GC cells, which remains to be confirmed.
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April-2015
Volume 33 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Impact Factor: 3.8
  • Ranked Oncology
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  • CiteScore: 8.5
  • CiteScore Rank: Q1: #74/404 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.719
  • SCImago Journal Rank (SJR): 0.864
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Spandidos Publications style
Yang X, Cai H, Liang Y, Chen L, Wang X, Si R, Qu K, Jiang Z, Ma B, Miao C, Miao C, et al: Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells. Oncol Rep 33: 1723-1730, 2015.
APA
Yang, X., Cai, H., Liang, Y., Chen, L., Wang, X., Si, R. ... Gao, P. (2015). Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells. Oncology Reports, 33, 1723-1730. https://doi.org/10.3892/or.2015.3757
MLA
Yang, X., Cai, H., Liang, Y., Chen, L., Wang, X., Si, R., Qu, K., Jiang, Z., Ma, B., Miao, C., Li, J., Wang, B., Gao, P."Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells". Oncology Reports 33.4 (2015): 1723-1730.
Chicago
Yang, X., Cai, H., Liang, Y., Chen, L., Wang, X., Si, R., Qu, K., Jiang, Z., Ma, B., Miao, C., Li, J., Wang, B., Gao, P."Inhibition of c-Myc by let-7b mimic reverses mutidrug resistance in gastric cancer cells". Oncology Reports 33, no. 4 (2015): 1723-1730. https://doi.org/10.3892/or.2015.3757