Circ_0039569 Competes with MARCKS for miR-133b Binding Sites to Promote the Progression of Renal Cell Carcinoma.

Peng Zhao, Jing Zhang

Nephron 2022

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The dysregulation of circular RNAs (circRNAs) has been shown to be correlated with the aggressiveness of renal cell carcinoma (RCC). Hence, this study investigated the role and mechanism of circ_0039569 in RCC progression. The levels of circ_0039569, miR-133b, and MARCKS (myristoylated alanine-rich protein kinase C substrate) were detected using quantitative real-time polymerase chain reaction and Western blot. In vitro experiments were conducted by using 5-ethynyl-2'-deoxyuridine assay, colony-formation assay, Transwell assay, flow cytometry, and Western blot. The direct interactions between miR-133b and circ_0039569 or MARCKS were verified by using dual-luciferase reporter and pull-down assays. Xenograft mice models were established to conduct in vivo analysis. Circ_0039569 was highly expressed in RCC tissues and cells. Functionally, silencing of circ_0039569 suppressed cell proliferation, migration, and invasion, but induced cell apoptosis in RCC cells in vitro. Moreover, mice subcutaneous xenograft assay suggested that circ_0039569 knockdown impeded tumor growth in vivo. Mechanistically, circ_0039569 acted as a sponge for miR-133b to regulate the expression of its target MARCKS. Importantly, miR-133b inhibition or MARCKS knockdown attenuated the anticancer effects of circ_0039569 knockdown on RCC growth. Diminished circ_0039569 restrains the growth and propagation of RCC cells via miR-133b/MARCKS axis, indicating an underlying effective therapeutic target for RCC patients. © 2022 S. Karger AG, Basel.

Citation

Peng Zhao, Jing Zhang. Circ_0039569 Competes with MARCKS for miR-133b Binding Sites to Promote the Progression of Renal Cell Carcinoma. Nephron. 2022;146(4):404-417