CircGRHL2 suppresses EMT and enhances sunitinib sensitivity in ccRCC via the miR-330-5p/FBXO21 axis

Clear cell renal cell carcinoma (ccRCC) is one of the most common cancers in the urinary system. Studies have shown that circRNAs have potential effects in a variety of human tumors. Studying the important signaling pathways and therapeutic targets of circRNAs is essential to increase understanding of ccRCC. In this present study, we clarified that hsa_circGRHL2 was dramatically decreased in ccRCC tissues and cells, which was closely related to the clinicopathological features of ccRCC patients. Functionally, circGRHL2 significantly inhibited the proliferation, migration, and invasion of ccRCC cells in vitro. Mechanistically, circGRHL2 sponges miR-330-5p, could regulate miR-330-5p to affect proliferation, migration, invasion of ccRCC cells and have effect on epithelial-mesenchymal transition (EMT). Moreover, FBXO21, could be a direct target of miR-330-5p, which further reducing P85 phosphorylation, inhibiting PI3K/Akt pathway activation, and weakening the EMT. In addition, circGRHL2 overexpression enhances the sensitivity of 769-P cells to sunitinib and enhances the ability of sunitinib treatment effects in vivo. In summary, we proposed a novel signaling network, in which circGRHL2 inhibited the progression of ccRCC via the miR-330-5p/FBXO21 axis and decreased PI3K/Akt activation.