MiR-200b/c-RAP1B axis represses tumorigenesis and malignant progression of papillary thyroid carcinoma through inhibiting the NF-κB/Twist1 pathway

Abstract

Papillary thyroid carcinoma (PTC) is a common endocrine malignancy with an increasing occurrence and recurrence. MicroRNAs (miRNAs) have been widely acknowledged to be participated in human cancers. However, how these miRNAs exert roles and potential mechanisms in PTC regulatory networks is still lacking. The purpose of our study lies in discovering the regulatory basis of miR-200b/c and Rap1b for PTC tumorigenesis and malignant progression, as well as the underlying molecular mechanisms. Herein, miR-200b/c expression was sharply dropped and Rap1b expression was up-regulated in PTC cells and tissues samples when compared to normal thyroid epithelial cells and normal tissues. miR-200b/c targeted Rap1 directly and negatively regulated its expression. miR-200b/c overexpression suppressed proliferative, colony forming, migratory and invasive capabilities and EMT as well as elevated apoptosis of PTC cells through inhibiting Rap1b. Furthermore, xenograft experiments showed miR-200b/c overexpression constrained growth of PTC xenograft and EMT. miR-200b/c inhibited NF-κB/Twist1 signals via regulating the Rap1b expression in cells and animal models. Taken together, our study suggested that upregulation of miR-200b/c-RAP1B axis constrained PTC cell proliferation, invasion, migration and EMT. Also, the upregulation of miR-200b/c-RAP1B leaded to elevated apoptosis through inhibiting the NF-κB/Twist1 pathway, thus inhibiting PTC tumorigenesis and malignant progression.