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Utilizing Functional Genomics Screening to Identify Potentially Novel Drug Targets in Cancer Cell Spheroid Cultures
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CircEIF3H-IGF2BP2-HuR scaffold complex promotes TNBC progression via stabilizing HSPD1/RBM8A/G3BP1 mRNA

Xiaojin Song1, Bing Chen2, Yiran Liang1

  • 1Department of Breast Surgery, Qilu Hospital of Shandong University, Jinan, Shandong Province, 250012, China.

Cell Death Discovery
|May 14, 2022
PubMed

Insights

A novel circular RNA, circEIF3H, promotes triple-negative breast cancer (TNBC) progression and metastasis. It acts as a scaffold protein, offering a potential new therapeutic target for TNBC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Triple-negative breast cancer (TNBC) presents a poor prognosis, with metastasis being a primary cause of treatment failure.
  • The role of circular RNAs (circRNAs) in TNBC progression remains incompletely understood.
  • Identifying novel molecular mechanisms driving TNBC is crucial for developing effective therapies.

Purpose of the Study:

  • To identify and characterize novel circRNAs involved in triple-negative breast cancer (TNBC) progression.
  • To elucidate the functional role and regulatory mechanism of the identified circRNA in TNBC.
  • To evaluate the potential of the novel circRNA as a therapeutic target for TNBC.

Main Methods:

  • High-throughput RNA sequencing of paired breast cancer and adjacent normal tissues.
  • In vitro and in vivo experimental models to assess TNBC proliferation and metastasis.
  • Biochemical assays to investigate the molecular mechanism of circRNA function.

Main Results:

  • A novel circRNA, circEIF3H, was discovered and found to be upregulated in breast cancer tissues.
  • High circEIF3H expression correlated with poor prognosis in TNBC patients.
  • circEIF3H was essential for TNBC proliferation and metastasis, functioning as a scaffold for IGF2BP2 and HuR to stabilize specific mRNAs.

Conclusions:

  • circEIF3H is a novel, cancer-promoting circRNA significantly upregulated in TNBC.
  • circEIF3H drives TNBC progression and metastasis by scaffolding IGF2BP2/HuR, independent of microRNA sponging.
  • circEIF3H represents a promising novel therapeutic target for individualized TNBC treatment.

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