Downregulated circPOKE promotes breast cancer metastasis through activation of the USP10-Snail axis

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer-related death among females. Metastasis accounts for the majority of BC related deaths. One feasible strategy to solve this challenging problem is to disrupt the capabilities required for tumor metastasis. Herein, we verified a novel metastasis suppressive circRNA, circPOKE in BC. circPOKE was downregulated in primary and metastatic BC tissues and overexpression of circPOKE inhibited the metastatic potential but not the proliferative ability of BC cells in vitro and in vivo. Mechanistically, circPOKE competitively binds to USP10, and reduces its binding to Snail, a key transcriptional regulator of EMT, thereby inhibiting Snail stability via the protein-ubiquitination degradation pathway. In addition, we found that circPOKE could be secreted into the extracellular space via exosomes and that exosome-carried circPOKE significantly inhibited the invasive capabilities of BC cells in vitro and in vivo. Furthermore, the levels of circPOKE, USP10 and Snail are clinically relevant in BC, suggesting that circPOKE may be used as a potential therapeutic target for patients with BC metastasis.

Automated summary

A novel metastasis suppressive circular RNA, circPOKE, has been identified in breast cancer. circPOKE binds to USP10 and reduces its binding to Snail, thereby affecting Snail stability and inhibiting the metastatic potential of breast cancer cells through the protein-ubiquitination degradation pathway. Additionally, circPOKE can be secreted into the extracellular space via exosomes and significantly inhibits the invasive capabilities of breast cancer cells. These findings suggest that circPOKE may serve as a potential therapeutic target for breast cancer metastasis.