POGZ targeted by LINC01355/miR-27b-3p retards thyroid cancer progression via interplaying with MAD2L2.

Despite the high morbidity of thyroid cancer (THCA), the underlying molecular pathology remains elusive. That autism-associated protein POGZ has recently been involved in tumorigenesis intrigues us exploring its relevant molecular regulatory network in THCA. Clinical characteristics and intermolecular relationships were dissected by bioinformatics. Interaction between POGZ and MAD2L2 was examined by Co-IP assay. Targeting relationships between miR-27b-3p and POGZ/LINC01355 was verified by sequence prediction and dual-luciferase reporter detection. Cellular effects of genes were assessed by CCK-8 assay, clone formation assay, and Transwell assay, and further confirmed by a tumor-bearing nude mice model. Our results demonstrated a decrease in POGZ expression in THCA tissues and cell lines, and an interaction between POGZ and MAD2L2 protein. POGZ inhibited both the proliferation and motility of THCA cells, with these effects being reversed upon MAD2L2 silencing. LINC01355 exhibited low expression level and a positive correlation with POGZ in THCA. Both miR-27b-3p and LINC01355 were identified as regulators of POGZ through targeting. Elevated miR-27b-3p suppressed POGZ expression. LINC01355 promoted POGZ and counteracted the inhibitory effects of miR-27b-3p. Furthermore, miR-27b-3p increased the proliferation and motility of THCA cells, an effect that was blocked by LINC01355. At the animal level, POGZ, LINC01355, and MAD2L2 all attenuated tumor growth in THCA. Collectively, POGZ restrains THCA growth by interacting with MAD2L2 protein, and POGZ modulation involves a complex interplay orchestrated by LINC01355-targeted miR-27b-3p. By reporting the first POGZ-focused ceRNA network involving noncoding RNA in THCA, our study paves the way for exploring POGZ-related pathways and developing new therapeutic strategies in cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-025-04231-7.