MicroRNA-198 inhibits metastasis of thyroid cancer by targeting H3F3A.

OBJECTIVE

This study was designed to investigate the role of microRNA-198 in thyroid cancer (TCa) progression.

PATIENTS AND METHODS

Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to examine microRNA-198 and H3F3A levels in tumor tissue specimens and paracancerous ones collected from 50 patients with TCa, and the interplay between microRNA-198 or H3F3A and some clinical indicators or prognosis of TCa patients was analyzed as well. MicroRNA-198 and H3F3A overexpression models were constructed using lentivirus in TCa cell lines TPC-1 and BHP2-7, and the impacts of microRNA-198 on TCa cell functions were evaluated by using cell counting kit-8 (CCK-8), plate clone formation, and transwell assays. Finally, recovery investigations were conducted to explore the underlying mechanisms as well as the interaction between microRNA-198 and H3F3A.

RESULTS

QRT-PCR indicated that in tumor tissues of TCa patients, microRNA-198 showed a remarkably lower expression than in adjacent normal tissue samples. Compared with patients with high expression of microRNA-198, those with microRNA-198 low expression had more advanced tumor stage, larger tumor size, higher lymph node metastasis rate, and lower overall survival rate. Meanwhile, the results of research on H3F3A were just opposite to the above observations on microRNA-198. In in vitro cell experiments, overexpression of microRNA-198 significantly weakened the proliferation and migration ability of thyroid tumor cells. Besides, Luciferase reporter gene experiment revealed that H3F3A was a specific target gene for microRNA-198. Moreover, qRT-PCR indicated that H3F3A and microRNA-198 were negatively correlated in thyroid carcinoma tissues. In addition, compared with NC group, overexpression of H3F3A markedly enhanced the migration and proliferative capacity of TCa cells. Lastly, recovery experiment revealed a mutual regulation between microRNA-198 and H3F3A, the two of which may together participate in the malignant progression of TCa.

CONCLUSIONS

MicroRNA-198 is remarkably reduced in TCa and inhibits malignant progression of TCa by regulating H3F3A. Meanwhile, microRNA-198 is remarkably associated with pathological stage, tumor size, lymph node metastasis, and poor prognosis of TCa.