A pleiotropic effect of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on insulin-like growth factor II, insulin-like growth factor-1 receptor and insulin-like growth factor-binding protein-3 in hepatocellular carcinoma

  • Authors:
    • Reem Amr Assal
    • Hend Mohamed El Tayebi
    • Karim Adel Hosny
    • Gamal Esmat
    • Ahmed Ihab Abdelaziz
  • View Affiliations

  • Published online on: February 24, 2015     https://doi.org/10.3892/mmr.2015.3382
  • Pages: 645-650
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Abstract

MicroRNAs (miRs) have a major role in the pathogenesis of hepatocellular carcinoma (HCC). As the insulin‑like growth factor (IGF) axis is a highly tumorigenic pathway in HCC, the present study attempted to target it with miRs. Potential targeting of crucial members of the IGF axis by miRNAs at the 3'-untranslated region (3'-UTR) was predicted using bioinformatic tools, such as microrna.org, Diana lab and Targetscan, while 5'-UTR targeting was predicted using bibiserv software. Expression profiling of obtained miRNAs was performed using quantitative polymerase chain reaction (qPCR) in 22 non‑metastatic HCC biopsy samples and 10 healthy tissues. To investigate the impact of miRNAs on their potential downstream targets, transfection of miRNAs was performed in HuH‑7 cells and the targets' expression was quantified using qPCR. Transcripts of insulin‑like growth factor‑1 receptor (IGF‑1R), insulin‑like growth factor binding protein‑3 (IGFBP‑3) and IGF‑II were found to be potentially targeted at the 5'-UTR and 3'-UTR regions by the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p. The two miRNAs showed a similar expression pattern in HCC tissues compared to those in healthy tissues. Forced expression of miR‑96‑5p and miR‑182‑5p in the HCC cell line HuH‑7 had inducing effects on IGFBP‑3 and IGF‑II transcripts. Of note, the two miRs had differential effects on IGF‑1R, where miR‑96‑5p induced IGF‑1R mRNA expression and miR‑182‑5p inhibited its expression. The present study revealed the pleiotropic impact of the single clustered hepatic metastamiRs miR‑96‑5p and miR‑182‑5p on IGF‑1R, and an inducing effect on IGF‑II and IGFBP‑3 in hepatocellular carcinoma.
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July-2015
Volume 12 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Assal RA, El Tayebi HM, Hosny KA, Esmat G and Abdelaziz AI: A pleiotropic effect of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on insulin-like growth factor II, insulin-like growth factor-1 receptor and insulin-like growth factor-binding protein-3 in hepatocellular carcinoma. Mol Med Rep 12: 645-650, 2015
APA
Assal, R.A., El Tayebi, H.M., Hosny, K.A., Esmat, G., & Abdelaziz, A.I. (2015). A pleiotropic effect of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on insulin-like growth factor II, insulin-like growth factor-1 receptor and insulin-like growth factor-binding protein-3 in hepatocellular carcinoma. Molecular Medicine Reports, 12, 645-650. https://doi.org/10.3892/mmr.2015.3382
MLA
Assal, R. A., El Tayebi, H. M., Hosny, K. A., Esmat, G., Abdelaziz, A. I."A pleiotropic effect of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on insulin-like growth factor II, insulin-like growth factor-1 receptor and insulin-like growth factor-binding protein-3 in hepatocellular carcinoma". Molecular Medicine Reports 12.1 (2015): 645-650.
Chicago
Assal, R. A., El Tayebi, H. M., Hosny, K. A., Esmat, G., Abdelaziz, A. I."A pleiotropic effect of the single clustered hepatic metastamiRs miR-96-5p and miR-182-5p on insulin-like growth factor II, insulin-like growth factor-1 receptor and insulin-like growth factor-binding protein-3 in hepatocellular carcinoma". Molecular Medicine Reports 12, no. 1 (2015): 645-650. https://doi.org/10.3892/mmr.2015.3382