Targeting oncogenic microRNAs from the miR-371~373 and miR-302/367 clusters in malignant germ cell tumours causes growth inhibition through cell cycle disruption.

Acknowledgements: We wish to thank Dr Mike Gait (Laboratory of Molecular Biology, Cambridge, UK) for technical assistance. We thank the CCLG Tissue Bank and CCLG Principal Treatment Centres for the collection and provision of tissue samples (under CCLG project numbers 2002 BS 03 and 2020 BS 02). The CCLG Tissue Bank is funded by Cancer Research UK and CCLG. Some tissues were acquired from the Human Research Tissue Bank at Cambridge University Hospitals NHS Foundation Trust, whom we must additionally thank for their provision of histological services, and which is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). ; Funder: We thank the CCLG Tissue Bank and CCLG Principal Treatment Centres for the collection and provision of tissue samples (under CCLG project numbers 2002 BS 03 and 2020 BS 02). The CCLG Tissue Bank is funded by Cancer Research UK and CCLG. Some tissues were acquired from the Human Research Tissue Bank at Cambridge University Hospitals NHS Foundation Trust, whom we must additionally thank for their provision of histological services, and which is supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). We are grateful for financial support from the Max Williamson Fund and from Christiane and Alan Hodson, in memory of their daughter Olivia. The funders were not involved in study design, data collection or interpretation, or decision to submit for publication. ; Funder: St. Baldrick’s Foundation (St. Baldrick’s Foundation, Inc) ; BACKGROUND: MiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant germ cell tumours (GCTs), regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six of eight microRNAs from these clusters contain the seed sequence 'AAGUGC', determining mRNA targeting. Here we sought to identify the significance of these observations by targeting these microRNAs functionally. METHODS: We targeted miR-371~373 and/or miR-302/367 clusters in ...