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The human RNA surveillance factor Up-frameshift 1 inhibits hepatic cancer progression by targeting MRP2/ABCC2

Hai Zhang1, Yina You1, Zhongliang Zhu2

  • 1Department of Gastroenterology, Huangshi Central Hospital, The Affiliated Hospital of Hubei Polytechnic University, Huangshi, 435000, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|May 30, 2017
PubMed

Insights

Up-frameshift 1 (UPF1) acts as a tumor suppressor in hepatocellular carcinoma (HCC). It enhances chemotherapy sensitivity by downregulating ABCC2, thereby inhibiting cancer stem cell properties and epithelial-mesenchymal transition.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The precise mechanisms of Up-frameshift 1 (UPF1) in hepatocellular carcinoma (HCC) require further elucidation.
  • Previous studies have partially indicated UPF1's involvement in HCC, but a comprehensive understanding of its function is lacking.

Purpose of the Study:

  • To investigate the role and underlying mechanisms of UPF1 in hepatocellular carcinoma (HCC).
  • To explore UPF1's impact on HCC cell sensitivity to sorafenib, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) and immunohistochemistry were used to assess UPF1 and ABCC2 expression levels.
  • Cell viability, apoptosis assays, and Western blotting were employed to evaluate the functional effects of UPF1.
  • Nonsense-mediated mRNA decay (NMD) assays were performed to understand the mechanism of ABCC2 regulation.

Main Results:

  • UPF1 expression was significantly decreased in HCC tissues and negatively correlated with MRP2/ABCC2 expression.
  • Overexpression of UPF1 increased HCC cell sensitivity to sorafenib, suppressed EMT, and reduced CSC-like properties.
  • UPF1 directly bound to ABCC2, enhancing NMD efficiency and leading to ABCC2 downregulation.

Conclusions:

  • UPF1 functions as a tumor suppressor in HCC by inhibiting ABCC2 expression, thereby suppressing CSC-like characteristics and EMT.
  • UPF1 enhances chemotherapeutic sensitivity in HCC, suggesting its potential as a therapeutic target for HCC patients.
Keywords:
EMTHepatocellular carcinomaMRP2/ABCC2Nonsense-mediated mRNA decayUPF1

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