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RBFOX3 Regulates the Chemosensitivity of Cancer Cells to 5-Fluorouracil via the PI3K/AKT, EMT and

Tianze Liu1,2, Xiaojun Wu1, Yizhuo Li1

  • 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|April 25, 2018
PubMed
Abstract

Insights

RBFOX3 protein levels impact hepatocellular carcinoma (HCC) sensitivity to 5-FU chemotherapy. Lowering RBFOX3 enhances 5-FU

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • RBFOX3 is an RNA-binding protein crucial for neuronal development.
  • The role of RBFOX3 in hepatocellular carcinoma (HCC) chemosensitivity remains uncharacterized.

Purpose of the Study:

  • To investigate the biological functions of RBFOX3 in HCC.
  • To determine the effect of RBFOX3 on HCC chemosensitivity to 5-fluorouracil (5-FU).

Main Methods:

  • Examined RBFOX3 expression in HCC cell lines and tissues.
  • Performed in vitro studies involving RBFOX3 knockdown and overexpression.
  • Utilized a mouse xenograft model to assess 5-FU chemosensitivity.
  • Investigated downstream signaling pathways including PI3K/AKT, EMT, and apoptosis pathways.

Main Results:

  • RBFOX3 expression is elevated in HCC.
  • RBFOX3 knockdown inhibited HCC proliferation and enhanced 5-FU efficacy, promoting apoptosis and inhibiting migration/invasion.
  • RBFOX3 overexpression reduced 5-FU efficacy, decreasing apoptosis and increasing proliferation, migration/invasion.
  • RBFOX3 knockdown synergized with 5-FU to inhibit HCC growth via PI3K/AKT and EMT pathways, activating apoptosis.
  • RBFOX3 was validated to regulate 5-FU cytotoxicity in vivo.

Conclusions:

  • RBFOX3 significantly regulates the chemosensitivity of HCC to 5-FU.
  • Targeting RBFOX3 presents a potential therapeutic strategy to enhance 5-FU treatment efficacy for HCC.
Keywords:
5-fuorouracil (5-FU)Hepatocellular carcinoma (HCC)Rbfox3

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