Exosomal miR-145-5p inhibits papillary thyroid cancer by targeting TPM3 and inactivating the PI3K-Akt pathway

Abstract

Within the present study, the objective was to investigate the effects of exosomal miR-145-5p on the proliferation, migration and invasion of papillary thyroid cancer (PTC) cells, and explore the molecular mechanism involved. Bioinformatics analyses based on numerous public databases were conducted to profile the expression of microRNA (miR)-145-5p and tropomyosin 3 (TPM3) in PTC and explore the associations between TPM3 expression, tumor stemness and immune infiltration. Exosomes were isolated and separately loaded with miR-145-5p mimics, miR-145-5p inhibitors or small interfering-TPM3. Cellular uptake assay verified that PTC cells could efficiently internalize these modified exosomes. After uptake of the exosomes, colony formation, EdU and Transwell assays were applied to assess cell proliferation, migration and invasion. Western blotting and reverse transcription-quantitative PCR were further performed to detect the expression levels of key proteins and genes involved in the PI3K-Akt signaling pathway. Results showed miR-145-5p expression was elevated in the plasma exosomes of patients with PTC but decreased in PTC tissues. TPM3 was notably upregulated in thyroid cancer and its expression was associated with lymph node metastasis, tumor stemness and immune cell infiltration. Both miR-145-5p overexpression and TPM3 knockdown inhibited the malignant phenotypes of PTC cells and downregulated the activity of the PI3K-Akt pathway. By contrast, miR-145-5p inhibitors reversed the above inhibitory effects. Overall, exosomal miR-145-5p suppresses PTC progression by targeting TPM3 and inhibiting the PI3K-Akt signaling pathway. The present finding provides a novel molecular target and theoretical foundation for targeted therapy of thyroid cancer.