MiR-34c-3p acts as a tumor suppressor gene in osteosarcoma by targeting MARCKS

Abstract

Previous studies have demonstrated that microRNA (miR)-34c-3p is important in human cancer progression. However, the function of MIR-34c-3p in osteosarcoma (OS) remains to be elucidated. In the present study, MIR-34c-3p level was measured by reverse transcription-quantitative polymerase chain reaction in OS tissues and the associated prognostic value for overall survival was determined. The function of MIR-34c-3p was examined in vitro and in vivo. A luciferase reporter assay was used to identify the targets of MIR-34c-3p. The results of the present study revealed that MIR-34c-3p was downregulated in OS tissues and cell lines, and decreased levels of MIR-34c-3p were associated with a high mortality rate in patients with OS. Furthermore, restoration of MIR-34c-3p expression reduced cell growth in vitro and suppressed tumorigenesis in vivo. Conversely, inhibition of MIR-34c-3p stimulated OS cell growth in vitro and in vivo. Myristoylated alanine-rich protein kinase C substrate (MARCKS) was identified as a direct target of MIR-34c-3p and its overexpression partly reversed the suppressive effects of MIR-34c-3p. Furthermore, MARCKS was revealed to be upregulated and inversely correlated with MIR-34c-3p levels in OS tissues. These data suggested that MIR-34c-3p acts as a tumor suppressor via regulation of MARCKS expression in OS progression and MIR-34c-3p may be a promising therapeutic target for this type of cancer.