Journal article
MicroRNA-21 is immunosuppressive and pro-metastatic via separate mechanisms
LH Chi, RSN Cross, RP Redvers, M Davis, S Hediyeh-zadeh, S Mathivanan, M Samuel, EC Lucas, K Mouchemore, PA Gregory, CN Johnstone, RL Anderson
Oncogenesis | Published : 2022
Open access
Abstract
MiR-21 was identified as a gene whose expression correlated with the extent of metastasis of murine mammary tumours. Since miR-21 is recognised as being associated with poor prognosis in cancer, we investigated its contribution to mammary tumour growth and metastasis in tumours with capacity for spontaneous metastasis. Unexpectedly, we found that suppression of miR-21 activity in highly metastatic tumours resulted in regression of primary tumour growth in immunocompetent mice but did not impede growth in immunocompromised mice. Analysis of the immune infiltrate of the primary tumours at the time when the tumours started to regress revealed an influx of both CD4+ and CD8+ activated T cells an..
View full abstractGrants
Awarded by National Breast Cancer Foundation
Funding Acknowledgements
The authors are grateful to Alejandro Urtreger (University of Buenos Aires) for providing the LM3 cells and to Andrei Goga (UCSF) for providing the pMSCVpuromiR-21 vector and the miR-21 reporter gene. We would also like to thank David Baloyan for assistance with the flow cytometry. This project was supported by a National Health and Medical Research Council of Australia (NHMRC) Project Grant (APP1020280) and from the Austin Medical Research Fund (2018). RLA was supported by a senior fellowship from NBCF. LHC is supported by a graduate research scholarship from La Trobe University. Olivia Newton-John Cancer Research Institute (Heidelberg, Australia) acknowledges the support of the Operational Infrastructure Program of Victorian Government.