MicroRNA-7 Exerts Antiangiogenic Effect on Colorectal Cancer via ERK Signaling

Xuepeng Fan1, Mei Liu2, Hao Tang2

  • 1Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Intensive Care Unit, Wuhan NO.1 Hospital, Wuhan, China.

Abstract

Insights

MicroRNA-7 (miR-7) suppresses colorectal cancer (CRC) angiogenesis by downregulating epidermal growth factor receptor (EGFR) via ERK signaling. This finding may offer new therapeutic targets for CRC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-7 (miR-7) family members are implicated in human cancer, influencing cell proliferation, apoptosis, migration, and invasion.
  • The specific role of miR-7 in colorectal cancer (CRC) requires further investigation.

Purpose of the Study:

  • To investigate the clinical significance of miR-7 in colorectal cancer (CRC).
  • To elucidate the biological function of miR-7 in CRC progression and angiogenesis.

Main Methods:

  • Analysis of microvascular density and expression of miR-7, EGFR, ERK1/2, VEGF, and TSP-1 in 76 CRC patient tissues.
  • Functional assays including ectopic expression, knockdown, reporter assays, MTT, scratch, Transwell, and flow cytometry to assess cell behavior and apoptosis.
  • Determination of vasculogenic mimicry density.

Main Results:

  • CRC tissues exhibited increased microvascular density, EGFR expression, activated ERK signaling, and downregulated miR-7.
  • EGFR was identified as a direct target gene of miR-7.
  • miR-7 overexpression and EGFR silencing reduced vasculogenic mimicry, migration, and invasion, while increasing apoptosis.
  • miR-7 and EGFR modulation affected TSP-1, EGFR, ERK1/2, and VEGF expression, with miR-7's effects being dependent on EGFR.

Conclusions:

  • Overexpressed miR-7 suppresses CRC cell angiogenesis by downregulating EGFR through the ERK signaling pathway.
  • miR-7's role in regulating EGFR presents potential new therapeutic targets for colorectal cancer treatment.

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