Suppression of MIR31HG affects the functional properties of thyroid cancer cells depending on the miR-761/MAPK1 axis

Abstract

Abstract Background Thyroid cancer is the most prevalent endocrine malignancy. Long non-coding RNA (lncRNA) MIR31HG is abnormally expressed in thyroid cancer tissues. However, the precise, critical role of MIR31HG in thyroid cancer development remains unclear. Methods MIR31HG, microRNA (miR)-761 and mitogen-activated protein kinase 1 (MAPK1) were quantified by quantitative real-time PCR (qRT-PCR) and immunoblotting. Cell viability, proliferation, apoptosis, invasion and migration abilities were evaluated by MTS, 5-Ethynyl-2′-Deoxyuridine (EdU), flow cytometry, transwell and wound-healing assays, respectively. Dual-luciferase reporter assays were used to validate the direct relationship between miR-761 and MIR31HG or MAPK1. Results MIR31HG was overexpressed in human thyroid cancer, and its overexpression predicted poor prognosis. Suppression of MIR31HG impeded cell proliferation, invasion and migration, as well as promoted cell apoptosis in vitro, and diminished the growth of xenograft tumors in vivo. Mechanistically, MIR31HG targeted and regulated miR-761. Moreover, miR-761 was identified as a molecular mediator of MIR30HG function in regulating thyroid cancer cell behaviors. MAPK1 was established as a direct and functional target of miR-761 and MAPK1 knockdown phenocopied miR-761 overexpression in impacting thyroid cancer cell behaviors. Furthermore, MIR31HG modulated MAPK1 expression by competitively binding to miR-761 via the shared binding sequence. Conclusion Our findings demonstrate that MIR31HG targets miR-761 to regulate the functional behaviors of thyroid cancer cells by upregulating MAPK1, highlighting a strong rationale for developing MIR31HG as a novel therapeutic target against thyroid cancer.