GSE169128
Targeted CRISPR interference and activation of microRNA-3662-HBP1 axis controls tumor progression of triple-negative breast cancer
MicroRNA-3662 (miR-3662) is not or very low expressed in normal human tissues but highly expressed in almost all types of human cancers, including breast cancer. However, the functional role of miR-3662 in human cancers remains a topic of debate. First, our bioinformatic analysis in the Cancer Genome Atlas dataset showed that miR-3662 expression is higher in triple-negative breast cancer (TNBC) and African American breast cancer than in other types of breast cancer. Next, we found that inhibition or knockout of endogenous mature miR-3662 in human TNBC cells suppresses cell proliferation and migration in vitro and tumor growth and metastasis in vivo. Functional analysis revealed that knockout of miR-3662 reduces the activation of Wnt/ß-catenin signaling in TNBC cells. Finally, using dual-luciferase assay, miRNA/mRNA immunoprecipitation assay, and CRISPR-mediated miR-3662 activation and repression, we further identified that HMG-box transcription factor 1 (HBP-1), a Wnt/ß-catenin signaling inhibitor, is a direct target of miR-3662 and is most likely responsible for miR-3662-mediated TNBC cell proliferation. Our results suggest that miR-3662 plays an oncogenic role in tumor progression and metastasis via a miR-3662-HBP1 axis, which negatively regulates Wnt /ß-catenin signaling pathway in TNBC cells. Overall design: total RNA expression by deep-sequencing in MDA-MB-231 sorted for different levels of miR-3662 activity