The miR-345-3p/PPP2CA signaling axis promotes proliferation and invasion of breast cancer cells

Breast cancer is the most common malignancy among women worldwide. Functional studies have demonstrated that miRNA dysregulation in many cases of cancer, in which miRNAs act as either oncogenes or tumor suppressor. Here we report that miR-345-3p is generally upregulated in breast cancer tissues and breast cancer cell lines. Overexpression and inhibition of miR-345-3p revealed its capacity in regulating proliferation and invasion of breast cancer cells. Further research identified protein phosphatase 2 catalytic subunit alpha (PPP2CA), a suppressor of AKT phosphorylation, as a candidate target of miR-345-3p. In vitro, miR-345-3p mimics promoted AKT phosphorylation by targeting its negative regulator, PPP2CA. Blocking miR-345-3p relieved its inhibition of PPP2CA, which attenuated PI3K-AKT signaling pathway. In vivo, inhibiting miR-345-3p by miR-345-3p-inhibition lentivirus suppressed tumor growth and invasiveness in mice. Together, the miR-345-3p/PPP2CA signaling axis exhibits tumor-promoting functions by regulating proliferation and invasion of breast cancer cells. These data provide a clue to novel therapeutic approaches for breast cancer.

Automated summary

This study found that miR-345-3p gene is upregulated in breast cancer tissues and cells, and its overexpression enhances the proliferation and invasion of breast cancer cells. The study also discovered that miR-345-3p promotes AKT phosphorylation by inhibiting protein phosphatase 2 catalytic subunit alpha (PPP2CA), and regulates the PI3K-AKT signaling pathway. Furthermore, inhibiting miR-345-3p can suppress tumor growth and invasiveness in mice.