Journal
ANTICANCER RESEARCH
Volume 38, Issue 9, Pages 5013-5026Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/anticanres.12820
Keywords
Pax-5; breast cancer; miRNA; miR-215-5p; EMT/MET
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Funding
- New Brunswick (NB) Innovation Foundation
- Canadian Breast Cancer Foundation
- Beatrice Hunter Cancer Research Institute
- Canadian Breast Cancer Society/QEII Foundation
- NB Health Research Foundation
- Terry Fox Strategic Health Research Training Program in Cancer Research at CIHR
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Background/Aim: In breast cancer, Pax-5 promotes pro-epithelial features and suppresses malignant cancer processes. However, the molecular mechanism of this antitumor activity remains largely unknown. This study aimed to identify the cellular roles of Pax-5-regulated miRNAs in breast cancer progression. Materials and Methods: After transient transfection of Pax-5 in MDA-MB-231 breast cancer cells, Pax5-regulated miRNA expression was examined by next-generation sequencing. The identified Pax-5-regulated miRNAs were then validated by qRT-PCR and examined for the roles they play in breast cancer cells. Results: Pax-5 was shown to be an effective modulator of miR-215-5p and its target genes. MiR-215 inhibited cell proliferation and migration of breast cancer cells, but not cell invasion. More importantly, Pax-5induced suppression of cancer cell proliferation and migration was found to be miR-215-dependent. Interestingly, miR-215 profiling in clinical tumor samples showed that miR-215 expression was lower in cancer tissues in comparison to healthy controls. Conclusion: Pax-5 reduces breast cancer proliferation and migration through up-regulation of the tumor suppressor miR-215. This result supports the use of miR-215 as a prognostic marker for breast cancer.
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