The /miR-491 Axis Modulates Papillary Thyroid Cancer Invasion and Metastasis Through TGM2/NFκb/FN1 Signaling

NEAT1 (nuclear paraspeckle assembly transcript 1) is an oncogenic long non-coding RNA (lncRNA) that facilitates tumorigenesis in multiple cancers. In papillary thyroid cancer (PTC), the molecular mechanism by which affects invasion and metastasis remains elusive. RNA sequencing was used to discover differentially expressed downstream genes. Protein and RNA expression analyses and immunohistochemistry detected the expression of , Transglutaminase 2 (TGM2), and microRNA-491 (miR-491) among PTC and non-cancerous tissues. Transwell and wound healing assays, and a mouse model of lung metastasis were used for further functional analyses. Bioinformatics was performed to predict miRNAs binding to both and . Rescue experiments and dual-luciferase reporter assays were performed. In PTC tissues, expression was markedly increased and regulated TGM2 expression. TGM2 was overexpressed in PTC, correlating positively with exthyroidal extension and lymph node metastasis. knockdown significantly inhibited invasion and metastasis. sponged miR-491, acting as a competing endogenous RNA to regulate expression. Fibronectin 1 (FN1) was predicted as a TGM2 target. TGM2 could transcriptionally activate FN1 by promoting nuclear factor kappa B (NFκb) p65 nuclear translocation, ultimately promoting PTC invasion/metastasis. These findings identify that sponges miR-491 to regulate TGM2 expression. TGM2 activates FN1 NFκb to promote PTC invasion and metastasis.