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Targeting the microRNA-21/AP1 axis by 5-fluorouracil and pirarubicin in human hepatocellular carcinoma

Xiaodong He1, Jingjing Li1, Weidong Guo2

  • 1Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, PR China.

Oncotarget
|December 30, 2014
PubMed

Insights

Low microRNA-21 levels predict better outcomes for hepatocellular carcinoma (HCC) patients receiving chemotherapy. Targeting microRNA-21 may enhance treatment efficacy, suggesting a new therapeutic strategy for HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNAs (miRNAs) act as oncomiRs or tumor suppressors in various cancers.
  • The predictive value of specific miRNAs for chemotherapy response remains unclear.
  • Hepatocellular carcinoma (HCC) is a significant global health concern.

Purpose of the Study:

  • To investigate the correlation between microRNA-21 expression and treatment outcomes in HCC patients undergoing hepatic arterial infusion chemotherapy (HAIC).
  • To explore the therapeutic potential of targeting microRNA-21 in HCC treatment.

Main Methods:

  • Analysis of microRNA-21 expression in HCC tumors.
  • Correlation of microRNA-21 levels with time to recurrence and disease-free survival.
  • In vivo studies using subcutaneous xenograft mouse models to assess the effect of microRNA-21 suppression combined with chemotherapy.
  • Investigation of the AP-1 and microRNA-21-mediated signaling axis.

Main Results:

  • Lower microRNA-21 expression in HCC tumors was associated with longer recurrence-free and disease-free survival.
  • Combined treatment of microRNA-21 suppression with 5-fluorouracil and pirarubicin inhibited tumor growth in mouse models.
  • The AP-1 and microRNA-21 axis was identified as a therapeutic target, with its deregulation promoting HCC cell growth.

Conclusions:

  • MicroRNA-21 is a chemotherapy-responsive molecule and a potential prognostic biomarker for HCC patients undergoing HAIC.
  • Targeting microRNA-21 can enhance the efficacy of chemotherapeutic drugs.
  • MicroRNA-21 suppression combined with HAIC presents a promising novel therapeutic strategy for HCC.

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