Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Bone and Soft Tissue, Zhengzhou Central Affiliated Hospital to Zhengzhou University, Zhengzhou, China.
Cell Cycle. 2020 May;19(10):1172-1185. doi: 10.1080/15384101.2020.1749465. Epub 2020 Apr 14.
: Osteosarcoma (OS) is the most common primary bone malignancy, it has a dismal prognosis and mainly affects the children and adolescents. Previous reports have demonstrated that aberrantly expressed KIAA1429 plays crucial roles in the carcinogenesis of several cancers, but its expression status and functional role in the progression of OS have not previously been investigated.: Immunohistochemistry (IHC) and western blotting were conducted to determine KIAA1429 expression status in OS. The relationship between KIAA1429 expression and OS prognosis was analyzed based on public database and tissue microarray (TMA). Cell proliferation ability was evaluated by CCK8, EdU and colony formation assays, and Transwell and wound healing potential were also assessed . Xenograft nude mouse model was performed to elucidate the tumor growth . The main specific miRNA targeting KIAA1429 in OS cells was identified.: KIAA1429 expression is markedly overexpressed in OS, and elevated KIAA1429 expression is significantly associated with an unfavorable prognosis. Functional investigations demonstrate that KIAA1429 silencing could attenuate proliferation, migration and invasion abilities of OS , as well as tumor growth . Mechanistically, microRNA-143-3p (miR-143-3p) was identified as the crucial specific mediator of KIAA1429 expression in OS cells. Furthermore, restoring KIAA1429 expression could partially reverse miR-143-3p mediated tumor-inhibition effects. Additionally, we found that knockdown of KIAA1429 or ectopic overexpression of miR-143-3p could repress stemness cell properties and the inhibition could be partly abolished by overexpression of KIAA1429.: In summary, this study establishes miR-143-3p/KIAA1429 axis as promising therapeutic target for OS patients.
骨肉瘤(OS)是最常见的原发性骨恶性肿瘤,预后不良,主要影响儿童和青少年。先前的报告表明,异常表达的 KIAA1429 在几种癌症的发生中起着关键作用,但它在 OS 进展中的表达状态和功能作用尚未被研究过。
免疫组织化学(IHC)和 Western blot 用于确定 OS 中 KIAA1429 的表达状态。根据公共数据库和组织微阵列(TMA)分析 KIAA1429 表达与 OS 预后的关系。通过 CCK8、EdU 和集落形成测定评估细胞增殖能力,还评估了 Transwell 和伤口愈合潜力。进行异种移植裸鼠模型以阐明肿瘤生长。确定 OS 细胞中针对 KIAA1429 的主要特定 miRNA。
KIAA1429 在 OS 中表达明显过表达,并且升高的 KIAA1429 表达与不良预后显著相关。功能研究表明,KIAA1429 沉默可减弱 OS 中增殖、迁移和侵袭能力以及肿瘤生长。机制上,microRNA-143-3p(miR-143-3p)被鉴定为 OS 细胞中 KIAA1429 表达的关键特异性介质。此外,恢复 KIAA1429 表达可部分逆转 miR-143-3p 介导的肿瘤抑制作用。此外,我们发现下调 KIAA1429 或过表达 miR-143-3p 可抑制干细胞特性,而过表达 KIAA1429 可部分消除抑制作用。
总之,本研究确立了 miR-143-3p/KIAA1429 轴作为骨肉瘤患者有前途的治疗靶点。