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CircKDM4B suppresses breast cancer progression via the miR-675/NEDD4L axis

Xiang-Yu Guo1,2, Tian-Tian Liu1,2, Wen-Jie Zhu1,2

  • 1Key Laboratory for Experimental Teratology of the Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.

Oncogene
|February 11, 2022
PubMed

Insights

Circular RNAs (circRNAs) like circKDM4B act as tumor suppressors in breast cancer. This novel circRNA inhibits cancer cell migration, invasion, and angiogenesis, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
  • Understanding the specific functions of circRNAs in breast cancer is crucial for identifying new therapeutic strategies.

Purpose of the Study:

  • To investigate the role of a novel circRNA, circKDM4B (hsa_circ_0002926), in breast cancer.
  • To explore its potential as a therapeutic target for breast cancer progression.

Main Methods:

  • Whole-transcriptome sequencing to identify circRNAs.
  • RT-qPCR and Sanger sequencing for validation.
  • In vitro cell assays (migration, invasion, HUVEC assays).
  • In vivo tumor growth and metastasis models.
  • Mechanistic studies involving microRNA sponging and protein ubiquitination.

Main Results:

  • circKDM4B was significantly downregulated in breast cancer tissues.
  • Overexpression of circKDM4B inhibited breast cancer cell migration, invasion, and tumor growth in vivo.
  • circKDM4B suppressed angiogenesis by inhibiting HUVEC migration and tube formation.
  • Mechanistically, circKDM4B sponges miR-675, leading to the downregulation of NEDD4L, PI3KCA ubiquitination, and subsequent inhibition of PI3K/AKT signaling and VEGFA secretion.

Conclusions:

  • circKDM4B functions as a tumor suppressor in breast cancer.
  • It plays a critical role in inhibiting angiogenesis and tumor metastasis.
  • circKDM4B represents a potential therapeutic target for breast cancer.

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