miRNA expression profiling regulates necroptotic cell death in hepatocellular carcinoma

  • Authors:
    • Maria Visalli
    • Marcello Bartolotta
    • Francesca Polito
    • Rosaria Oteri
    • Adalberto Barbera
    • Roberto Arrigo
    • Rosa Maria Di Giorgio
    • Giuseppe Navarra
    • M'hammed Aguennouz
  • View Affiliations

  • Published online on: May 17, 2018     https://doi.org/10.3892/ijo.2018.4410
  • Pages: 771-780
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Abstract

Hepatocellular carcinoma (HCC) is one of the most aggressive types of cancer and is among the leading causes of cancer-related mortality worldwide. Although the dysregulation of microRNAs (miRNAs or miRs) has often been reported in HCC, the precise molecular mechanisms by which miRNAs modulate the process of tumorigenesis and the behavior of cancer cells are not yet clearly understood. In this study, we identified a novel three‑miRNA signature, including miR‑371-5p, miR‑373 and miR‑543, that appears to orchestrate programmed cell necrosis in HCC by directly targeting the caspase‑8 gene (Casp‑8). Our results demonstrated that miR‑371-5p, miR‑373 and miR‑543 were overexpressed in HCC tissues compared with paired adjacent normal tissues. The upregulation of these miRNAs specifically and markedly downregulated the expression of Casp‑8, as well as significantly enhanced the Z-VAD/TNF‑α-induced necroptosis of HCC cells. By contrast, the selective knockdown of miRNA expression led to a significant increase in Casp‑8 levels and a marked reduction in programmed cell necrosis. Intriguingly, the sustained overexpression of Casp‑8 reversed the pro‑necroptotic effects exerted by miRNA mimics. Finally, a strong inverse association between the level of miR‑223 and the expression levels of nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing-3 inflammasome was observed in our HCC specimens. On the whole, the present study revealed a molecular link between the three‑miRNA signature, comprising miR‑371-5p, miR‑373 and miR‑543, and the negative necroptotic regulator Casp‑8, and presents evidence for its employment as a novel potential diagnostic, prognostic and therapeutic target in HCC.
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August-2018
Volume 53 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Visalli M, Bartolotta M, Polito F, Oteri R, Barbera A, Arrigo R, Di Giorgio RM, Navarra G and Aguennouz M: miRNA expression profiling regulates necroptotic cell death in hepatocellular carcinoma. Int J Oncol 53: 771-780, 2018
APA
Visalli, M., Bartolotta, M., Polito, F., Oteri, R., Barbera, A., Arrigo, R. ... Aguennouz, M. (2018). miRNA expression profiling regulates necroptotic cell death in hepatocellular carcinoma. International Journal of Oncology, 53, 771-780. https://doi.org/10.3892/ijo.2018.4410
MLA
Visalli, M., Bartolotta, M., Polito, F., Oteri, R., Barbera, A., Arrigo, R., Di Giorgio, R. M., Navarra, G., Aguennouz, M."miRNA expression profiling regulates necroptotic cell death in hepatocellular carcinoma". International Journal of Oncology 53.2 (2018): 771-780.
Chicago
Visalli, M., Bartolotta, M., Polito, F., Oteri, R., Barbera, A., Arrigo, R., Di Giorgio, R. M., Navarra, G., Aguennouz, M."miRNA expression profiling regulates necroptotic cell death in hepatocellular carcinoma". International Journal of Oncology 53, no. 2 (2018): 771-780. https://doi.org/10.3892/ijo.2018.4410