microRNAs (miRNAs) regulate gene expression and are critical in cancer initiation and progression. This study examined the in vitro and in vivo effects of miR-29b-3p in papillary thyroid carcinoma (PTC). Quantitative RT-PCR revealed that miR-29b-3p expression was significantly downregulated in PTC tissues compared with adjacent normal thyroid tissue, with reduced expression strongly associated with advanced tumor-node-metastasis (TNM) stage (p < 0.001).

In in vitro functional assays, overexpression of miR-29b-3p suppressed PTC cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT), while silencing it enhanced these processes. COL1A1 and COL5A1 were identified as direct targets of miR-29b-3p. Both genes were overexpressed in PTC tissue, and their reintroduction reversed the inhibitory effects of miR-29b-3p, confirming their mechanistic role.

In a murine xenograft model, treatment with a miR-29b-3p agomir significantly reduced tumor growth, supporting its tumor-suppressive function in vivo. Collectively, these findings demonstrate that miR-29b-3p inhibits PTC progression primarily through in vitro suppression of proliferation, invasion, and EMT by targeting COL1A1 and COL5A1, with complementary in vivo evidence of tumor growth inhibition.