Liu Hongliang, Su Pengxiao, Zhi Liqiang, Zhao Kai
Department of Foot and Ankle Surgery, Xi'an Honghui Hospital, Xi'an, Shanxi 710054, P.R. China.
Department of Surgery, Xi'an Honghui Hospital, Xi'an, Shanxi 710054, P.R. China.
Mol Med Rep. 2017 Mar;15(3):1204-1210. doi: 10.3892/mmr.2017.6108. Epub 2017 Jan 11.
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.
先前的研究表明,微小RNA(miR)-34c-3p在人类癌症进展中具有重要作用。然而,miR-34c-3p在骨肉瘤(OS)中的功能仍有待阐明。在本研究中,通过逆转录-定量聚合酶链反应检测了OS组织中miR-34c-3p的水平,并确定了其对总生存期的相关预后价值。在体外和体内研究了miR-34c-3p的功能。采用荧光素酶报告基因测定法鉴定miR-34c-3p的靶标。本研究结果显示,miR-34c-3p在OS组织和细胞系中表达下调,miR-34c-3p水平降低与OS患者的高死亡率相关。此外,miR-34c-3p表达的恢复可降低体外细胞生长并抑制体内肿瘤发生。相反,抑制miR-34c-3p可在体外和体内刺激OS细胞生长。肉豆蔻酰化富含丙氨酸的蛋白激酶C底物(MARCKS)被鉴定为miR-34c-3p的直接靶标,其过表达部分逆转了miR-34c-3p的抑制作用。此外,MARCKS在OS组织中上调,且与miR-34c-3p水平呈负相关。这些数据表明,miR-34c-3p通过调控MARCKS表达在OS进展中发挥肿瘤抑制作用,miR-34c-3p可能是这类癌症的一个有前景的治疗靶点。