Department of Orthopedics, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Orthopedics, Shanghai Songjiang District Central Hospital, Shanghai, China.
Bioengineered. 2022 Apr;13(4):8174-8186. doi: 10.1080/21655979.2021.1982305.
Osteosarcoma (OS) is the most common high-grade malignant bone tumor in teenagers. MicroRNAs can function as posttranscriptional regulators of gene expression, playing critical roles in cancer dev-877-3p in OS. Quantitative real-time RT-PCR was carried out for detecting miR-877-3p expression in OS. The effects of miR-877-3p on proliferation was analyzed via MTT, colony formation, and flow cytometry assays. Angiogenesis of endothelial cells were investigated by wound healing and tube formation assay. Gene profiling based on PCR array and luciferase reporter assay were conducted to determine target genes of miR-877-3p. In-vivo study was used to determine the effects of miR-877-3p on the tumor growth. The expression of miR-877-3p was markedly downregulated in OS tissues and cell lines. Low expression of miR-877-3p predicts poor prognosis of OS patients. miR-877-3p overexpression was found to inhibit the proliferation of OS cell lines. The angiogenesis assays showed that miR-877-3p attenuated the angiogenesis. Further mechanism studies showed that miR-877-3p can reduce (Fibroblast Growth Factor 2) FGF2 expression in OS cells by binding to the 3'UTR end of FGF2. Moreover, increased expression of miR-877-3p was responsible for the inhibition of tumor growth and angiogenesis. Taken together, our findings indicated that miR-877-3p might exhibit tumor suppressive role by targeting FGF2 signaling, which may serve as potential target for OS.
骨肉瘤（OS）是青少年中最常见的高级恶性骨肿瘤。microRNAs 可以作为基因表达的转录后调节剂，在癌症发生发展中发挥重要作用。在 OS 中检测 miR-877-3p 的表达。通过 MTT、集落形成和流式细胞术分析检测 miR-877-3p 对增殖的影响。通过划痕愈合和管形成测定研究内皮细胞的血管生成。基于 PCR 阵列和荧光素酶报告基因测定进行基因谱分析，以确定 miR-877-3p 的靶基因。进行体内研究以确定 miR-877-3p 对肿瘤生长的影响。miR-877-3p 在 OS 组织和细胞系中的表达明显下调。miR-877-3p 低表达预示着 OS 患者预后不良。发现过表达 miR-877-3p 可抑制 OS 细胞系的增殖。血管生成测定表明 miR-877-3p 可通过与 FGF2 的 3'UTR 末端结合来减弱血管生成。此外，miR-877-3p 的表达增加导致肿瘤生长和血管生成受到抑制。总之，我们的研究结果表明，miR-877-3p 通过靶向 FGF2 信号通路发挥肿瘤抑制作用，可能成为 OS 的潜在靶点。
