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是一种参与透明细胞肾细胞癌免疫微环境的预后生物标志物,并与从G1期到S期的转变相关。

is a prognostic biomarker involved in immune microenvironment of clear cell renal cell carcinoma and associated with the transition from G1 phase to S phase.

作者信息

Yao Huibao, Lyu Feifei, Ma Jian, Sun Fengze, Tang Gonglin, Wu Jitao, Zhou Zhongbao

机构信息

Department of Urology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.

Department of Traditional Chinese Medicine, The Sixth Medical Center of PLA General Hospital, Beijing, China.

出版信息

Front Oncol. 2023 Jan 26;13:1035321. doi: 10.3389/fonc.2023.1035321. eCollection 2023.

DOI:10.3389/fonc.2023.1035321
PMID:36776322
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9909346/
Abstract

BACKGROUND

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the world and affects human health seriously. is a mitotic regulator which is essential to the metaphase-to-anaphase transition in cell cycle. Although plays a crucial role in the malignant progression of tumors, there are few reports on its role in ccRCC.

METHODS

The transcriptional expression profile and clinical data of were downloaded from TCGA database and verified by qRT-PCR. Kaplan-Meier plotter was used to analyze the effect of on overall survival (OS), disease specific survival (DSS) and progression-free interval (PFI) of patients with ccRCC. Univariable and multivariable Cox regression analysis were used to determine the independent prognostic factors of ccRCC. The effects of on cell migration and invasion were detected by wound healing assay and transwell invasion assay, and CCK-8 assay, colony formation assay and cell cycle assay were used to detect the effect of on cell proliferation. In addition, the changes in cell cycle related proteins were detected by western blot.

RESULTS

was highly expressed in human ccRCC and was positively correlated with pathologic stage, TNM stage and histologic grade. In addition, patients with high expression of had a poor prognosis. Univariable and multivariable Cox regression analysis identified that was an independent prognostic factor of ccRCC. Additionally, was also closely related to immune cell infiltration. Experiments identified that the knockdown of could significantly inhibit the proliferation, migration and invasion abilities of ccRCC. The expression of cyclin D1, CDK4 and CDK6 was also significantly reduced after knockdown.

CONCLUSIONS

plays a vital role in the development of ccRCC and may become a potential therapeutic target in the future.

摘要

背景

透明细胞肾细胞癌(ccRCC)是全球最常见的肿瘤之一,严重影响人类健康。[蛋白名称]是一种有丝分裂调节因子,对细胞周期中从中期到后期的转变至关重要。尽管[蛋白名称]在肿瘤的恶性进展中起关键作用,但关于其在ccRCC中的作用报道较少。

方法

从TCGA数据库下载[蛋白名称]的转录表达谱和临床数据,并通过qRT-PCR进行验证。使用Kaplan-Meier绘图仪分析[蛋白名称]对ccRCC患者总生存期(OS)、疾病特异性生存期(DSS)和无进展生存期(PFI)的影响。采用单变量和多变量Cox回归分析确定ccRCC的独立预后因素。通过伤口愈合试验和Transwell侵袭试验检测[蛋白名称]对细胞迁移和侵袭的影响,使用CCK-8试验、集落形成试验和细胞周期试验检测[蛋白名称]对细胞增殖的影响。此外,通过蛋白质印迹法检测细胞周期相关蛋白的变化。

结果

[蛋白名称]在人类ccRCC中高表达,与病理分期、TNM分期和组织学分级呈正相关。此外,[蛋白名称]高表达的患者预后较差。单变量和多变量Cox回归分析确定[蛋白名称]是ccRCC的独立预后因素。此外,[蛋白名称]还与免疫细胞浸润密切相关。实验确定敲低[蛋白名称]可显著抑制ccRCC的增殖、迁移和侵袭能力。敲低[蛋白名称]后,细胞周期蛋白D1、细胞周期蛋白依赖性激酶4(CDK4)和细胞周期蛋白依赖性激酶6(CDK6)的表达也显著降低。

结论

[蛋白名称]在ccRCC的发生发展中起重要作用,未来可能成为潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0851/9909346/c0ebc38db634/fonc-13-1035321-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0851/9909346/9f17195fde48/fonc-13-1035321-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0851/9909346/9e6fbd575df6/fonc-13-1035321-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0851/9909346/2b3ad5e42c1a/fonc-13-1035321-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0851/9909346/9ef96bf78eec/fonc-13-1035321-g009.jpg
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