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Updated: Jul 15, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
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Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes

Shivani Bailey1,2, Marta Ferraresso1, Luz Alonso-Crisostomo1

  • 1Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.

British Journal of Cancer
|October 3, 2023
PubMed
Abstract

Insights

Over-expressed microRNAs (miR-371~373 and miR-302/367) are key drivers in malignant germ cell tumours (GCTs). Targeting these microRNAs with LNA-DNA inhibitors effectively inhibited GCT cell growth by disrupting cell cycle regulation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Germ cell tumours (GCTs) consistently over-express miR-371~373 and miR-302/367 clusters across all subtypes and patient demographics.
  • These microRNA clusters share a common 'AAGUGC' seed sequence critical for mRNA targeting.

Purpose of the Study:

  • To investigate the functional significance of miR-371~373 and miR-302/367 clusters in malignant GCTs.
  • To identify effective therapeutic strategies by targeting these microRNAs.

Main Methods:

  • Utilized CRISPR-Cas9, gapmer, PNA, and LNA-DNA inhibition techniques to target miR-371~373 and miR-302/367 clusters in GCT cell lines.
  • Performed functional assays to assess the impact of microRNA targeting on cell growth and molecular pathways.

Main Results:

  • LNA-DNA based inhibition of miR-302/367 cluster microRNAs led to significant growth inhibition in seminoma and YST cells.
  • Targeting resulted in de-repression of mRNAs regulated by the 'AAGUGC' seed sequence, impacting Rho-GTPase signaling, vesicle transport, and cell cycle.
  • Confirmed direct cell cycle effects, including G0/G1 phase arrest and S-phase reduction.

Conclusions:

  • Specific targeting of miR-371~373 and miR-302/367 microRNAs is functionally significant in malignant GCTs.
  • Growth inhibition in GCTs is mediated through the disruption of cell cycle regulation by these microRNAs.

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