CircSPAG16 suppresses cadmium-induced transformation of human bronchial epithelial cells by decoying PIP5K1α to inactivate Akt.

Abstract

Circular RNAs (circRNAs) have been implicated to have important regulatory functions in chemical carcinogenesis via sponging microRNAs to regulate gene expression. Our study revealed a novel mechanism of circRNA in cadmium carcinogenesis through directly binding with protein. Here, we used cadmium-transformed human bronchial epithelial BEAS-2B cells to study the involvement and mechanism of circRNA in lung carcinogenesis caused by cadmium. By high-throughput sequencing, circSPAG16 was identified to be the most significantly downregulated circRNA in cadmium-transformed cells. CircSPAG16 was downregulated at Week 8, 12, 16, and 20 during cadmium-induced cell transformation. In addition, circSPAG16 overexpression prevented cadmium-induced transformation of BEAS-2B cells. Mechanistically, circSPAG16 inhibited the function of phosphatidylinositol 4-phosphate 5-kinase type-1 α (PIP5K1α) by binding with it. We demonstrated that PIP5K1α acted as an oncogene to activate Akt and promoted cancer hallmarks including proliferation, migration, invasion, and anchorage-independent growth in cadmium-transformed cells. CircSPAG16 overexpression inactivates PIP5K1α/Akt signaling in the transformed cells. Furthermore, PIP5K1α overexpression significantly rescued the inhibitory effects of circSPAG16 overexpression on pAkt and cancer hallmarks in cadmium-transformed cells. Collectively, our results revealed that circSPAG16 could prevent cadmium-induced transformation through binding with PIP5K1α to inactivate Akt. These results provide a novel regulatory mechanism of circRNA into carcinogenesis induced by cadmium.