Asterosaponin CN-3 performs an anti-glioma effect by inhibiting the migration and invasion of glioma cells through the regulation of miR-4465/HMGA1/NF-κB signaling pathway

Malignant gliomas are devastating tumors that frequently kill patients within 1 year of diagnosis. Diffuse invasion is a major obstacle to cure, which allows tumor to escape from complete surgical resection as well as chemotherapy and radiotherapy. Therefore, the development of new chemotherapeutic agent that inhibiting the infiltrative growth of glioma is urgently needed. Culcita novaeguineae-3 (CN-3) is a marine-derived steroidal saponin which exhibit significant cytotoxicity to glioma cells. This study was designed to confirm the effect of CN-3 on glioma and to further clarify its mechanism of action. The experimental results showed that CN-3 could significantly inhibit the proliferation, invasion and migration of glioma cells in vitro and in vivo. CN-3 could down-regulate the expression of high mobility group protein A1 (HMGA1), to inhibit the infiltrative growth of glioma cells. Furthermore, the metastatic mobility was significantly reduced in HMGA1 knockout glioma cells. Moreover, miR-4465 was confirmed to target and reduce HMGA1 expression. In addition, CN-3 could upregulate the expression of miR-4465 in cells, thereby inhibiting migration and invasion of glioma cells. These results elucidate the mechanism by which CN-3, a steroidal saponin from the sea, may inhibit the invasive behavior of glioma cells through the miRNA-4465/HMGA1/NF-κB pathway, which also raise the prospect of using CN-3 as a chemotherapeutic agent to prevent glioma invasive growth.