CircPFKP orchestrates a novel competing endogenous RNA network to regulate SPRY4/p38-MAPK signaling and modulate papillary thyroid carcinoma aggressiveness.

Papillary thyroid carcinoma (PTC) is one of the most common malignancies of the head and neck, with a rising incidence worldwide. Circular RNAs (circRNAs), a type of noncoding RNAs (ncRNAs) found abundantly in cells and tissues, have been demonstrated to be crucial regulators in cancer initiation and progression. However, the molecular functions of circRNAs in PTC remain largely unexplored. In this study, we identified circPFKP as a significantly dysregulated circRNA by mining clinical databases and demonstrated its important role in PTC progression. Even with its elevated expression, we found silencing of circPFKP markedly promoted the proliferation, migration, and invasion of PTC cells in vitro. Through bioinformatics analysis and dual-luciferase reporter assays, we confirmed that circPFKP acts as a sponge for miR-4516, thereby upregulating the expression of SPRY4. Enhanced SPRY4 inhibited tumor cell proliferation and migration while simultaneously reducing tumor cell sensitivity to pro-apoptotic factors in the tumor microenvironment, primarily by suppressing the p38 MAPK signaling pathway. Collectively, our study is the first to uncover the biological function of circPFKP in PTC and highlights its potential as a novel therapeutic target for PTC patients.