CACNA1C-AS2 inhibits cell proliferation and suppresses cell migration and invasion via targeting FBXO45 and PI3K/AKT/mTOR pathways in glioma.

Glioma is the most common brain cancer with a poor prognosis, and its underlying molecular mechanisms still needs to be further explored. In the current study, we discovered that an antisense lncRNA, CACNA1C-AS2, suppressed growth, migration and invasion of glioma cells, suggesting that CACNA1C-AS2 functions as a tumor suppressor. Furthermore, we found that CACNA1C-AS2 negatively regulated Fbxo45 protein expression in glioma cells. Impressively, extensive experimental results revealed that Fbxo45 accelerated growth, migration and invasion of glioma cells. Clinically, increased Fbxo45 expression was observed in 75 human glioma tissue samples. Moreover, in vivo experiments also demonstrated that Fbxo45 overexpression enhanced tumor growth in mice. Especially, we further identified that Fbxo45 activated mTORC1 rather than mTORC2 through PI3K/AKT signaling to promote cell growth and motility in glioma cells. Rescue experiments also exhibited that CACNA1C-AS2 inhibited cell growth and motility partly through down-regulating Fbxo45 expression in glioma. Our results provide the novel insights into the critical role of CACNA1C-AS2/Fbxo45/mTOR axis involved in regulating glioma tumorigenesis and progression, and further indicate that CACNA1C-AS2 and Fbxo45 may be the potential biomarkers and therapeutic targets for glioma.