circPPP2R4 promotes colorectal cancer progression and reduces ROS production through the miR-646/FOXK1 axis

Circular RNAs (circRNAs) play important roles in colorectal cancer (CRC) development and progression. This study aimed to investigate the function and molecular mechanism of circPPP2R4 in CRC. Based on bioinformatic analyses and validation by qRT-PCR, we identified a novel circRNA, circPPP2R4, which was upregulated in CRC tissues. Receiver operating characteristic curve analysis implied a high diagnostic value of circPPP2R4 for CRC. Additionally, high circPPP2R4 levels were positively correlated with advanced clinical stage and lymph node metastasis. Functionally, circPPP2R4 overexpression facilitated CRC cells proliferation, migration and invasion, whereas circPPP2R4 knockdown attenuated the malignant behaviors. In mouse models, circPPP2R4 overexpression remarkably promoted tumor growth and lung metastasis. Mechanistically, a series of experiments containing RIP, RNA pull-down, and dual-luciferase reporter assays revealed the circPPP2R4/miR-646/FOXK1 axis in CRC. Further experiments were conducted to verify that circPPP2R4 reduced reactive oxygen species generation to exert its oncogenic function by sponging miR-646 to upregulate FOXK1 expression. For the first time, we identified the regulatory role of circPPP2R4 in CRC pathogenesis, providing a potential diagnostic biomarker and therapeutic strategy for CRC.

Automated summary

This study identified a novel circRNA, circPPP2R4, that is upregulated in colorectal cancer (CRC) and is associated with advanced clinical stage and lymph node metastasis. Functional experiments showed that circPPP2R4 overexpression promotes CRC cell proliferation, migration, and invasion, while circPPP2R4 knockdown attenuates these malignant behaviors. Mechanistic studies revealed the circPPP2R4/miR-646/FOXK1 axis in CRC, providing a potential diagnostic biomarker and therapeutic strategy for CRC.