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circRAD18 sponges miR-208a/3164 to promote triple-negative breast cancer progression through regulating IGF1 and FGF2

Yutian Zou1, Shaoquan Zheng1, Weikai Xiao1

  • 1Department of Breast Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Carcinogenesis
|April 20, 2019
PubMed

Insights

Circular RNAs (circRNAs), like circRAD18, are key regulators in triple-negative breast cancer (TNBC). This study reveals circRAD18 promotes TNBC progression by sponging microRNAs, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are emerging as critical regulators in various cancers, but their specific roles in triple-negative breast cancer (TNBC) remain largely unknown.
  • Understanding the mechanisms of circRNAs in TNBC is crucial for developing novel diagnostic and therapeutic strategies.

Purpose of the Study:

  • To investigate the function and mechanism of hsa_circ_0002453 (circRAD18) in the occurrence and progression of triple-negative breast cancer (TNBC).
  • To identify circRAD18 as a potential prognostic biomarker and therapeutic target for TNBC.

Main Methods:

  • Microarray analysis to identify differentially expressed circRNAs in TNBC tissues and cell lines.
  • Functional assays including proliferation, colony formation, migration, and apoptosis assays.
  • Mouse xenograft models to evaluate the in vivo role of circRAD18.
  • Luciferase reporter assays to confirm the interaction between circRAD18, microRNAs, and target genes.

Main Results:

  • CircRAD18 expression is significantly upregulated in TNBC tissues and cell lines and correlates with advanced TNBC stages.
  • Knockdown of circRAD18 inhibits TNBC cell proliferation, migration, and tumor growth while promoting apoptosis.
  • CircRAD18 functions as a competing endogenous RNA (ceRNA) by sponging miR-208a and miR-3164, leading to the upregulation of IGF1 and FGF2.
  • The circRAD18-miR-208a/3164-IGF1/FGF2 axis plays a pivotal role in TNBC tumorigenesis and metastasis.

Conclusions:

  • CircRAD18 is a key oncogenic circRNA that promotes TNBC progression through the ceRNA mechanism involving miR-208a/3164 and IGF1/FGF2.
  • CircRAD18 serves as a potential prognostic biomarker and a promising therapeutic target for TNBC treatment.

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