MicroRNA-582-5p promotes triple-negative breast cancer invasion and metastasis by antagonizing CMTM8

Abstract

ABSTRACT Triple-negative breast cancer (TNBC) commonly have aggressive properties. microRNA-582-5p (miR-582-5p) modulates the progression of several cancers. Yet, the role of miR-582-5p in TNBC progression is undetermined. In the current study, we investigated miR-582-5p expression levels and clinical significance in TNBC. The impact of miR-582-5p modulation on the biological behaviors of TNBC cells were measured. The downstream gene(s) regulated by miR-582-5p in TNBC was explored. We showed that compared to adjacent normal breast tissues, the miR-582-5p level was elevated in TNBC samples. The upregulation of miR-582-5p correlated with lymph node metastasis. Overexpression of miR-582-5p enhanced TNBC cell migration and invasion, whereas knockdown of miR-582-5p had an adverse impact on aggressive phenotype. In vivo xenograft mouse studies demonstrated that miR-582-5p overexpression accelerated TNBC growth and metastasis. Mechanistically, miR-582-5p selectively inhibited CMTM8, leading to a reduction of CMTM8 expression. CMTM8 showed suppressive effects on TNBC cell migration and invasion. Rescue experiments revealed that overexpression of CMTM8 impaired miR-582-5p-induced migration and invasion in TNBC cells. Overall, our data uncover an oncogenic role for miR-582-5p in TNBC metastasis through inhibition of CMTM8. We suggest miR-582-5p as a promising target for managing TNBC.