Upregulation of miR-421 predicts poor prognosis and promotes proliferation, migration, and invasion of papillary thyroid cancer cells.

Abstract

Background:Papillary thyroid carcinoma (PTC) represents the most frequent subtype of thyroid cancer (TC) with poor prognosis mainly due to the severe invasion and metastasis. As an oncogene, microRNA-421 (miR-421) is involved in the development of various cancers. This study was to investigate the clinical significance of miR-421 in PTC and its effects on the biological function of PTC cells.Methods:The expression level of miR-421 in all tissues and PTC cell lines was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Subsequently, the relationship between miR-421 expression and the clinicopathological feature was detected by chi-square analysis in 106 patients with PTC. In addition, Kaplan-Meier and multivariate Cox regression analysis were used to detect the survival time and the prognostic value of miR-421. Finally, the regulatory effect of miR-421 on the proliferation, migration, and invasion ability of PTC cells was detected by Cell Counting Kit (CCK-8) and Transwell assay.Results:Compared with all control groups, the expression of miR-421 was significantly increased in 106 patients tissues and PTC cell lines (p < 0.001). In addition, patients with miR-421 upregulated in PTC showed more positive lymph node metastasis (p = 0.011), positive tumor infiltration (p = 0.031), and TNM stage III/IV (p = 0.019), and when miR-421 expression level was elevated, the survival rate of PTC patients was poor (log-rank test, p = 0.023). Furthermore, miR-421 might be an independent prognostic biomarker for PTC (hazard ratio [HR] = 3.172, 95% CI = 1.071-9.393, p = 0.037). Finally, increased levels of miR-421 can significantly promote cell proliferation, migration, and invasion (p < 0.01).Conclusion:miR-421 is a novel oncogene of PTC and is a valuable prognostic biomarker. Moreover, the upregulation of miR-421 enhances the proliferation, migration, and invasion of PTC cells.