MiR-1256 inhibits cell proliferation and cell cycle progression in papillary thyroid cancer by targeting 5-hydroxy tryptamine receptor 3A.

Abstract

Aberrant expression of miR-1256 has been reported to be closely associated with the development and progression of tumors, including colon cancer and lung cancer. However, study of its expression pattern and functional role in papillary thyroid cancer (PTC) is rare. Using quantitative real time PCR analysis, we found miR-1256 was significantly down-regulated in PTC tissues and cell lines. The correlation of miR-1256 expression with clinicopathological features was statistically analyzed. The results showed miR-1256 expression was significantly correlated with tumor size (p = 0.0124) and TNM stage (p = 0.0032). Restoring miR-1256 expression significantly inhibited proliferation and cell cycle progression of PTC cells demonstrated by CCK-8 and flow cytometry assays. Luciferase reporter assay and biotin-avidin pull-down assay showed miR-1256 can directly target 5-hydroxytryptamine receptor 3A (HTR3A) in PTC cells. The expression of miR-1256 was inversely correlated with HTR3A expression in PTC tissues. Knockdown of HTR3A imitated the suppressive effects of miR-1256 in PTC cells. Ectopic expression of HTR3A can antagonize the effects of miR-1256 on PTC cells. Furthermore, the suppressive effects of miR-1256 on the expression of PCNA, CDK4, Cyclin D1, and p21 were partially reversed by HTR3A overexpression in PTC cells. In summary, our data suggested that miR-1256 could suppress PTC cellular function by targeting HTR3A, which might be a potential therapeutic target for patients with PTC.