Oncoprotein 18 (OP18) is a recognized oncoprotein upregulated in various solid tumors. OP18 promotes microtubule disassembly and modulates tumor growth and migration activity. However, the mechanisms associated with genetic regulation of OP18 are yet to be elucidated. In the current study, we identified OP18 as a target gene of thyroid hormone (T3) in the HepG2 hepatoma cell line using microarray analysis.
The expression profiles and transcriptional mechanism of T3-suppressed OP18 were analyzed by molecular biology protocols. To verify if T3-regulated OP18 plays a functional role in liver tumorigenesis, OP18 knockdown tumor cell was generated and tumorigenicity was assessed.
OP18 mRNA and protein expression levels were significantly suppressed in the presence of T3. Thyroid hormone receptor directly targeted the OP18 upstream element to regulate transcriptional activity. Furthermore, thyroid hormone receptor expression was negatively correlated with OP18 in a portion of clinical hepatocellular carcinoma (HCC) specimens. Specific knockdown of OP18 suppressed cell proliferation and xenograft tumor growth in mice. In addition, cell cycle distribution was altered, with increased G2 and reduced G1 phases, in OP18 knockdown cells.
Our results suggest that oncogenic OP18 is transcriptionally downregulated by T3 in liver. This T3-mediated suppression of STMN supports the theory that the thyroid hormone plays an inhibitory role in HCC tumor growth, and lack of TR expression or regulation may lead to elevated OP18 expression and malignant growth.
Clinical trial identification
All authors have declared no conflicts of interest.