MiR-298 suppresses the malignant progression of osteosarcoma by targeting JMJD6.

Abstract

To explore the role of microRNA-298 (miR-298) in affecting biological characteristics of osteosarcoma cells, and the possible molecular mechanism. Fifty clinical cases of osteosarcoma were collected for detecting differential expressions of miR-298 using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and its level in osteosarcoma cell lines was determined as well. Proliferative and migratory changes in MG63 and U2OS cells overexpressing miR-298 were assessed by Cell Counting Kit-8 (CCK-8), transwell and wound healing assay. Candidate targets of miR-298 were predicted using online databases, and JMJD6, the most optimal target, was specifically analyzed by Dual-Luciferase reporter assay and rescue experiments. MiR-298 was both expressed in osteosarcoma and healthy bone tissues, which was lowly expressed in the former tissues. It was downregulated in osteosarcoma cell lines as well. Low level of miR-298 predicted higher incidences of lymphatic metastasis, distant metastasis, and lower overall survival and progression-free survival in osteosarcoma. Overexpression of miR-298 weakened proliferative and migratory changes in MG63 and U2OS cells. JMJD6 was confirmed as the target gene binding miR-298, and negatively correlated to miR-298 level in osteosarcoma tissues. Overexpression of JMJD6 reversed the effect of overexpressed miR-298 on alleviating the malignant progression of osteosarcoma. MiR-298 is less abundant in osteosarcoma samples, which is correlated to metastasis and prognosis of osteosarcoma. MiR-298, serving as a tumor suppressor, weakens proliferative and migratory abilities of osteosarcoma cells.