MicroRNA372 promotes breast cancer cell growth and metastasis by targeting LATS2

Objective: Several microRNAs (miRNAs) have been shown to play important roles in the generation and development of breast cancer (BC) tumors. miRNA-372 (miR-372), has been shown to be indispensable for various human malignancies. However, the role of miR-372 in BC is unknown. Methods: The expression of miR-372 was assessed in two BC cells lines, BT549 and SKBr3, and in BC tissue samples by real-time reverse transcription polymerase chain reaction (qRT-PCR). Then, the effects of miR-372 on cell proliferation, the cell cycle, apoptosis, and invasion were determined using human BC cells. A luciferase reporter assay was performed to confirm the target of miR-372. Western blotting was used to determine the protein changes that occur in response to miR-372. Then, the in vivo role of miR-372 was explored using an SKBr3 tumor xenograft model. Results: Upregulation of miR-372 was observed in the tested BC cell lines and tissues. Conversely, downregulation of miR-372 not only remarkably suppressed cell proliferation and invasion but also triggered G1/S cell cycle arrest. Mouse xenograft models showed that miR-372 knockdown inhibited BC tumor growth. Moreover, we found that miR-372 regulated the expression of large tumor suppressor kinase 2 (LATS2) by directly targeting its 3'-UTR. We also observed a negative correlation between miR-372 expression and LATS2 expression in BC specimens. Silencing of LATS2 was able to restore the suppressive effect of a miR-372 inhibitor. Finally, knockdown of miR-372 suppressed the phosphorylation of proteins in the PI3K/Akt pathway. Conclusions: These findings indicate that the oncogenic effect of miR-372 in BC is mediated by targeting LATS2.