敲除 KNTC1 可通过 MCM2 抑制骨肉瘤细胞的增殖和迁移。

IF 3 2区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Carcinogenesis Pub Date : 2024-08-01 Epub Date: 2024-05-31 DOI:10.1002/mc.23748
Lei Zhong, Yuanwei Dong, Shuqin Liu
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引用次数: 0

摘要

骨肉瘤(Osteosarcoma,OS)是一种常见的原发性恶性骨肿瘤,有必要进一步研究OS进展的分子机制。本研究通过免疫组化、定量 PCR(qPCR)和 Western 印迹检测了动点相关蛋白 1(KNTC1)和迷你染色体维护 2(MCM2)的表达。此外,还建立了异种移植模型,以探讨 KNTC1 下调在体内的影响。通过公共数据库和生物信息学分析筛选下游分子,确定MCM2在癌症中的表达。KNTC1在OS组织中过表达,并与OS患者的总生存率呈正相关。敲除 KNTC1 可抑制细胞的增殖、迁移、G2 期停滞并诱导细胞凋亡。此外,KNTC1 的下调还限制了异种移植肿瘤的形成。MCM2是共表达基因之一,在肉瘤中高表达,在KNTC1敲除后下调。MCM2 的过表达增强了 OS 细胞的增殖和迁移能力,从而逆转了 KNTC1 的抑制作用。KNTC1在OS中过表达,并通过上调MCM2促进OS的进展。
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KNTC1 knockdown inhibits the proliferation and migration of osteosarcoma cells by MCM2.

Osteosarcoma (OS) is a common primary malignant bone tumor, and it is necessary to further investigate the molecular mechanism of OS progression. The expression of kinetochore associated protein 1 (KNTC1) and minichromosome maintenance 2 (MCM2) was detected by immunohistochemistry, quantitative PCR (qPCR) and Western blot. Gene knockdown or overexpression cell models were constructed and the proliferation, apoptosis, cell cycle and migration were detected in vitro, besides, xenograft models were established to explore the effects of KNTC1 downregulation in vivo. Public databased and bioinformatics analysis were performed to screen the downstream molecules and determine the expression of MCM2 in cancers. KNTC1 was overexpressed in OS tissues and positively correlated with overall survival of OS patients. KNTC1 knockdown inhibited the proliferation and migration, and arrested G2 phase, and induced apoptosis. Besides, KNTC1 downregulation restricted the xenograft tumor formation. MCM2, one of the coexpressed genes, was highly expressed in sarcoma and downregulated after KNTC1 knockdown. MCM2 overexpression heightened the proliferation and migration ability of OS cells, which was reversed the inhibiting effects of KNTC1 knockdown. KNTC1 was overexpressed in OS and promoted the progression of OS by upregulating MCM2.

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来源期刊
Molecular Carcinogenesis
Molecular Carcinogenesis 医学-生化与分子生物学
CiteScore
7.30
自引率
2.20%
发文量
112
审稿时长
2 months
期刊介绍: Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.
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