Tumor Cell-Derived Exosomal circ-PRKCI Promotes Proliferation of Renal Cell Carcinoma via Regulating miR-545-3p/CCND1 Axis.

Simple Summary: The morbidity and mortality of renal cell carcinoma (RCC) remain high, and there is an urgent need to explore the reliable biomarker and molecular mechanism of RCC. Circ-PRKCI is a novel circRNA discovered in recent years, and has been confirmed to participate in tumor progression by acting as an miRNA sponge. However, the role of circ-PRKCI in RCC remains unclear. Here, with the aid of an online bioinformatics database and luciferase reporter assays, we found that circ-PRKCI could bind to miR-545-3p, while CCND1 served as a target of miR-545-3p. Caki-1-derived exosomes could thus inhibit miR-545-3p expression via the upregulation of circ-PRKCI. Through a series of functional experiments, we confirmed that Caki-1-derived exosomal circ-PRKCI promoted RCC proliferation by regulating the miR-545-3p/CCND1 axis. Our study will provide new insights for RCC clinical treatment. Renal cell carcinoma (RCC) originates from the epithelial cells of the renal tubules and has a high degree of malignancy and heterogeneity. Recent studies have found that exosomes regulate intercellular communication via transferring various bioactive molecules, such as circular RNAs (circRNAs), which are critical for cancer progression. However, the role of tumor cell-derived exosomal circRNAs in RCC remains unclear. In this study, we reported the high expression of circ-PRKCI in RCC tissues and serum exosomes. We also found that circ-PRKCI could be transferred exosomally from highly malignant RCC cells to relatively less malignant RCC cells. Tumor cell-derived exosomal circ-PRKCI promoted the proliferation, migration, and invasion of RCC cells, while inhibiting their apoptosis. Mechanistically, we found that circ-PRKCI promoted the proliferation of RCC via the miR-545-3p/CCND1 signaling pathway. Our study is the first to report the potential mechanisms of tumor cell-derived exosomal circ-PRKCI in RCC. In conclusion, this study will provide a new understanding about the molecular mechanisms of RCC progression. [ABSTRACT FROM AUTHOR]