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Circular RNA circHIPK2 inhibits colon cancer cells through miR-373-3p/RGMA axis

Jie Lun1, Yuying Zhang2, Mengchao Yu3

  • 1Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao Cancer Institute, Qingdao University, Qingdao, 266071, China; School of Pharmacy, Qingdao University, Qingdao, 266071, China.

Cancer Letters
|May 18, 2024
PubMed

Insights

Circular RNAs (circRNAs) like circHIPK2 are downregulated in colon cancer, promoting tumor growth. circHIPK2 inhibits cancer via the miR-373-3p/RGMA/BMP pathway, offering potential therapeutic strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) play roles in cancer, but their specific functions and regulation are not fully understood.
  • Colon cancer progression involves complex molecular alterations, necessitating the identification of novel biomarkers and therapeutic targets.

Purpose of the Study:

  • To investigate the role and mechanism of circHIPK2 in colon cancer development.
  • To explore the regulatory relationship between HOXD10, circHIPK2, and colon cancer progression.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to measure circHIPK2 and HOXD10 expression.
  • In vitro assays (proliferation, migration, invasion) and in vivo tumor xenograft models.
  • Mechanism studies involving RNA immunoprecipitation (RIP) and luciferase reporter assays to elucidate the circHIPK2/miR-373-3p/RGMA axis.

Main Results:

  • circHIPK2 was significantly downregulated in colon cancer tissues and correlated with advanced tumor grade and poor survival.
  • HOXD10, a transcription factor, was found to regulate circHIPK2 expression and was also downregulated in colon cancer.
  • Low circHIPK2 expression promoted colon cancer cell proliferation, migration, invasion, tumor growth, and metastasis by sponging miR-373-3p to upregulate RGMA and activate BMP/Smad signaling.

Conclusions:

  • circHIPK2 acts as a tumor suppressor in colon cancer, inhibiting cell proliferation, migration, invasion, and metastasis.
  • The circHIPK2/miR-373-3p/RGMA/BMP signaling pathway represents a novel mechanism in colon cancer.
  • circHIPK2 holds potential as a prognostic biomarker and therapeutic target for colon cancer.
Keywords:
Circular RNAColon cancerMetastasisMicroRNATumor growth

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