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Updated: Aug 28, 2025

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
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Silencing circFTO inhibits malignant phenotype through modulating DUSP4 expression in clear cell renal cell carcinoma

Chen Yang1,2,3, Yiwen Zang4,5, Siqi Wu4,5,6

  • 1Huashan Hospital, Fudan University, Shanghai, China. YangC_Huashan@163.com.

Cell Death Discovery
|September 20, 2022
PubMed

Insights

Circular RNA circFTO promotes clear cell renal cell carcinoma (ccRCC) progression by inhibiting tumor suppressor miR-514b-3p, leading to DUSP4 overexpression and pathway activation. This circFTO/miR-514b-3p/DUSP4 axis is a potential therapeutic target for ccRCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer.
  • Circular RNAs (circRNAs) are increasingly recognized for their roles in various cancers, including kidney cancer.
  • Understanding the specific functions of circRNAs in ccRCC pathogenesis is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of circFTO in ccRCC development and progression.
  • To elucidate the molecular mechanism underlying circFTO's function in ccRCC.
  • To evaluate circFTO as a potential biomarker and therapeutic target for ccRCC.

Main Methods:

  • High-throughput sequencing and tissue microarrays were used to detect circFTO expression in ccRCC tissues.
  • In vitro and in vivo experiments were conducted to assess the effects of circFTO on ccRCC cell proliferation and invasiveness.
  • Mechanistic studies involved analyzing the interaction between circFTO, miR-514b-3p, and DUSP4, as well as downstream signaling pathways like KRAS/ERK and epithelial-mesenchymal transition (EMT).

Main Results:

  • CircFTO was found to be significantly upregulated in ccRCC tissues and correlated with a more aggressive tumor phenotype.
  • Upregulated circFTO was shown to sponge and inhibit miR-514b-3p, a known tumor suppressor.
  • CircFTO overexpression led to DUSP4 upregulation, KRAS/ERK pathway activation, increased EMT, and inhibited autophagy, ultimately promoting ccRCC cell proliferation and invasiveness.

Conclusions:

  • The circFTO/miR-514b-3p/DUSP4 axis plays a critical role in the development and progression of ccRCC.
  • CircFTO acts as an oncogenic circRNA by regulating the miR-514b-3p/DUSP4 pathway.
  • CircFTO represents a promising potential biomarker and therapeutic target for ccRCC treatment.

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