Second Clinical Medical College, Shanxi Medical University, Taiyuan, ShanXi, China.
Department of Orthopaedics, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Bioengineered. 2022 Apr;13(4):8915-8925. doi: 10.1080/21655979.2022.2056693.
MicroRNA-200c (miR-200c) generally acts as a tumor suppressor in multiple cancer types and a promising therapeutic target in tumorigenesis. However, only a few studies have explained the role of miR-200c in the development of osteosarcoma (OS). In this study, we investigated the role of miR-200c in OS progression and identified the regulatory pathway protein NDN involved in inhibiting the occurrence and development of OS. Firstly, we found that miR-200c is downregulated in OS cells and tissues. As well, and experiments showed that upregulating miR-200c inhibits the proliferation, invasion, metastasis of Saos-2 cells, promotes the apoptosis of Saos-2 cells and suppresses tumor growth in mice, indicating miR-200c plays a major role in regulating the OS progression. Furthermore, bioinformatics analysis showed that an anti-tumor protein, necdin (NDN), might be a potential target by miR-200c. To verify this hypothesis, we measured the expression level of NDN in OS cells and tissues and found NDN is downregulated, suggesting NDN is functional in OS progression. Moreover, we found that the expression levels of NDN and miR-200c in and experiments were positively correlated. However, the results of dual-luciferase reporter gene experiment showed miR-200c does not directly act on the 3' untranslated region (UTR) of NDN gene, indicating that NDN might be an important pathway protein which regulates OS progression in the presence of miR-200c. Therefore, miR-200c/NDN could be potential targets for developing effective treatment against OS.
微小 RNA-200c(miR-200c)通常在多种癌症类型中作为肿瘤抑制因子发挥作用,是肿瘤发生中的一个有前途的治疗靶点。然而,只有少数研究解释了 miR-200c 在骨肉瘤(OS)发展中的作用。在这项研究中,我们研究了 miR-200c 在 OS 进展中的作用,并确定了参与抑制 OS 发生和发展的调节途径蛋白 NDN。首先,我们发现 miR-200c 在 OS 细胞和组织中下调。同样,和实验表明,上调 miR-200c 抑制 Saos-2 细胞的增殖、侵袭和转移,促进 Saos-2 细胞的凋亡,并抑制小鼠肿瘤生长,表明 miR-200c 在调节 OS 进展中起主要作用。此外,生物信息学分析表明,抗肿瘤蛋白,necdin(NDN)可能是 miR-200c 的一个潜在靶标。为了验证这一假设,我们测量了 OS 细胞和组织中 NDN 的表达水平,发现 NDN 下调,表明 NDN 在 OS 进展中起作用。此外,我们发现和实验中 NDN 和 miR-200c 的表达水平呈正相关。然而,双荧光素酶报告基因实验的结果表明 miR-200c 不能直接作用于 NDN 基因的 3'非翻译区(UTR),表明 NDN 可能是 miR-200c 存在时调节 OS 进展的重要途径蛋白。因此,miR-200c/NDN 可能是开发针对 OS 有效治疗方法的潜在靶点。