CircSP3 encodes SP3-461aa to promote ccRCC progression via stabilizing MYH9 and activating the PI3K-Akt signaling pathway

Clear cell renal cell carcinoma (ccRCC) is a primary kidney cancer with high aggressive phenotype and extremely poor prognosis. Accumulating evidence suggests that circular RNAs (circRNAs) play pivotal roles in the occurrence and development of various human cancers. However, the expression, clinical significance and regulatory role of circRNAs in ccRCC remain largely unclear. Here we report that circSP3 to be increased in tissues from ccRCC patients and ccRCC cells, and to positively correlate with ccRCC malignant features. Knockdown of circSP3 inhibits proliferation, triggers apoptosis, and reduces migration and invasion in different ccRCC cells in vitro. Correspondingly, circSP3 overexpression Promote ccRCC tumorigenicity in a mouse xenograft model. Mechanistically, circSP3 could bind with the ribosome to initiate the translation process to encodes a novel 461-amino acid peptide referred to as SP3-461aa, which protects the MYH9 protein from proteasomal degradation. SP3-461aa played a pivotal role in mediating the oncogenic effects of circSP3 by interacting with the MYH9 protein and activating the PI3K-Akt signaling pathway. These findings suggested that circSP3 plays an important role in ccRCC development and could be a potential biomarker for the treatment and prognosis of ccRCC.