MiR-181c suppresses triple-negative breast cancer tumorigenesis by targeting MAP4K4

Breast cancer (BC) ranks as the highest incidence among cancer types in women all over the world. Triple-negative breast cancer (TNBC) is known as a highly aggressive subtype of BC due to high rate of recurrence and metastasis, poor prognosis and lacking of effective targeted therapies. MicroRNAs (miRNAs) are a class of short endogenous non-coding RNA that mostly functioning to silence the target mRNAs. In this study, we found miR-181c-5p (miR-181c) was down-expressed in TNBC tissues and cell lines, whereas MAP4K4 was highly-expressed. Up-regulation of miR-181c inhibited TNBC cells proliferation and migration, promoted TNBC cells apoptosis and regulated the cell cycle by arresting cells in the G0/G1 cell phase, while depletion of miR-181c showed opposite effect. Importantly, miR-181c suppressed MAP4K4 expression at both mRNA and protein levels by directly targeting MAP4K4, thereby inhibiting the tumor-promoting effect of MAP4K4. This study is the first to demonstrate the miR-181c/MAP4K4 signaling in suppressing TNBC, providing a novel therapeutic target for TNBC.