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Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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Regulation of MRP4 Expression by circHIPK3 via Sponging miR-124-3p/miR-4524-5p in Hepatocellular Carcinoma

Haihong Hu1,2, Yu Wang1,2, Zhiyuan Qin1,2

  • 1Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Cancer Center of Zhejiang University, Hangzhou 310058, China.

Biomedicines
|May 5, 2021
PubMed

Insights

Circular RNA circHIPK3 regulates multidrug resistance-associated protein 4 (MRP4) by sponging miR-124-3p and miR-4524-5p. This mechanism impacts MRP4 protein levels, offering insights into hepatocellular carcinoma (HCC) drug resistance.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Oncology

Background:

  • Multidrug resistance-associated protein 4 (MRP4) is an ATP-binding cassette transporter involved in cellular efflux, communication, and drug distribution.
  • MicroRNAs (miRNAs) are known to downregulate MRP4 expression, but the role of circular RNAs (circRNAs) remains unclear.

Purpose of the Study:

  • To investigate the regulatory role of circRNAs in MRP4 expression, particularly in hepatocellular carcinoma (HCC).
  • To elucidate the interaction between circHIPK3, specific miRNAs, and MRP4 in HCC.

Main Methods:

  • Computational prediction, luciferase reporter assays, and miRNA transfection were used to study miRNA-MRP4 interactions.
  • CircRNA in vivo precipitation assays were employed to confirm circHIPK3 binding to miR-124-3p and miR-4524-5p.
  • Knockdown and cotransfection experiments assessed the functional impact of circHIPK3 and miRNA interactions on MRP4 expression.

Main Results:

  • MRP4 was significantly upregulated in HCC tissues compared to adjacent noncancerous tissues.
  • miR-124-3p and miR-4524-5p reduced MRP4 protein levels, but not mRNA levels.
  • circHIPK3 acted as a competing endogenous RNA (ceRNA), binding to miR-124-3p and miR-4524-5p, thereby regulating MRP4 protein expression.

Conclusions:

  • circHIPK3 regulates MRP4 expression by sponging miR-124-3p and miR-4524-5p.
  • miR-4524-5p directly downregulates MRP4 expression.
  • These findings offer novel insights into preventing MRP4-related proliferation and multidrug resistance in HCC.
Keywords:
MRP4circHIPK3hepatocellular carcinomamiR-124-3pmiR-4524-5pmultidrug resistance

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