Open Access

IGF2BP3 and miR191‑5p synergistically increase HCC cell invasiveness by altering ZO‑1 expression

  • Authors:
    • Yuan Gao
    • Tianping Luo
    • Xiwu Ouyang
    • Chunfu Zhu
    • Junqiang Zhu
    • Xihu Qin
  • View Affiliations

  • Published online on: May 30, 2020     https://doi.org/10.3892/ol.2020.11693
  • Pages: 1423-1431
  • Copyright: © Gao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Early studies have indicated that insulin‑like growth factor II mRNA binding protein 3 (IGF2BP3/IMP3) may affect the progression of hepatocellular carcinoma (HCC); however, the detailed underlying mechanisms, particularly its linkage to tight junction protein‑mediated cell invasion, remain unclear. The present study revealed that IGF2BP3 increased HCC cell invasiveness by suppressing zonula occludens‑1 (ZO‑1) expression, via direct binding to the 3' untranslated region (3'‑UTR). Analysis of the molecular mechanisms demonstrated that IGF2BP3 binds to the overlapping targets of IGF2BP3‑RNA cross‑linkage and microRNA (miR)191‑5p targeting sites, and promotes the formation of an miR191‑5p‑­induced RNA‑induced silencing complex. The knockdown of IGF2BP3 or the addition of a miR‑191‑5p inhibitor decreased cellular invasiveness and increased ZO‑1 expression. Analysis of the human HCC database also confirmed the association between IGF2BP3 and HCC progression. Collectively, these preclinical findings suggest that IGF2BP3 increases HCC cell invasiveness by promoting the miR191‑5p‑induced suppression of ZO‑1 signaling. This newly identified signaling effect on small molecule targeting may aid in the development of novel strategies with which to inhibit HCC progression more effectively.

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August-2020
Volume 20 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Gao, Y., Luo, T., Ouyang, X., Zhu, C., Zhu, J., & Qin, X. (2020). IGF2BP3 and miR191‑5p synergistically increase HCC cell invasiveness by altering ZO‑1 expression. Oncology Letters, 20, 1423-1431. https://doi.org/10.3892/ol.2020.11693
MLA
Gao, Y., Luo, T., Ouyang, X., Zhu, C., Zhu, J., Qin, X."IGF2BP3 and miR191‑5p synergistically increase HCC cell invasiveness by altering ZO‑1 expression". Oncology Letters 20.2 (2020): 1423-1431.
Chicago
Gao, Y., Luo, T., Ouyang, X., Zhu, C., Zhu, J., Qin, X."IGF2BP3 and miR191‑5p synergistically increase HCC cell invasiveness by altering ZO‑1 expression". Oncology Letters 20, no. 2 (2020): 1423-1431. https://doi.org/10.3892/ol.2020.11693