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Rcl1抑制肝细胞癌的肿瘤进展:生物信息学与体外实验的综合分析

Rcl1 suppresses tumor progression of hepatocellular carcinoma: a comprehensive analysis of bioinformatics and in vitro experiments.

作者信息

Jiaze Yu, Sinan Hou, Minjie Yang, Yongjie Zhou, Nan Du, Liangwen Wang, Wen Zhang, Jianjun Luo, Zhiping Yan

机构信息

Department of Interventional Radiology, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, China.

National Clinical Research Center for Interventional Medicine, 180 Fenglin Road, Shanghai, 200032, China.

出版信息

Cancer Cell Int. 2022 Mar 9;22(1):114. doi: 10.1186/s12935-022-02533-x.

DOI:10.1186/s12935-022-02533-x
PMID:35264160
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8905783/
Abstract

BACKGROUND

RNA 3'-terminal phosphate cyclase-like protein (Rcl1) is involved in pre-rRNA processing, but its implication in cancers remains unclear.

METHODS

RCL1 expressions in 21 malignancies was examinated through GEPIA website portal. Clinical implication data related to RCL1 level in Hepatocellular Carcinoma (HCC) samples were downloaded through TCGA, ICGC, GEO databases. Survival analysis and gene function enrichment analyses were performed through R software. The correlation between RCL1 expression and tumor immune infiltration was assessed via the TIMER2.0 database. The effects of Rcl1 overexpression or knockdown on cell growth and metastasis was evaluated by CCK8, transwell, and cell cycle assays.

RESULTS

RCL1 expression is commonly down-regulated in HCC. The lower expression of RCL1 is associated with higher tumor stage, higher AFP level, vascular invasion, and poor prognosis. RCL1 expression has a significant correlation with immune cells infiltration in HCC, especially myeloid-derived suppressor cell (MDSC). Moreover, it was further identified that Rcl1 expression was reduced in HCC cell lines and negatively correlated with invasion of HCC cell lines. Immunofluorescence (IF) analysis revealed that the level of Rcl1 expression in the cytoplasm of HCC cells is significantly lower than that in the cytoplasm of L-02 cell. Moreover, both gain- and loss-of-function studies demonstrated that Rcl1 inhibited the growth and metastasis of HCC cells and regulated cell cycle progression in vitro.

CONCLUSIONS

Rcl1 may serve as a novel tumor suppressor in HCC, and its biological effect needs further study.

摘要

背景

RNA 3'-末端磷酸环化酶样蛋白(Rcl1)参与前体核糖体RNA(pre-rRNA)加工,但其在癌症中的作用仍不清楚。

方法

通过GEPIA网站门户检测21种恶性肿瘤中RCL1的表达。通过TCGA、ICGC、GEO数据库下载与肝细胞癌(HCC)样本中RCL1水平相关的临床意义数据。通过R软件进行生存分析和基因功能富集分析。通过TIMER2.0数据库评估RCL1表达与肿瘤免疫浸润之间的相关性。通过CCK8、transwell和细胞周期分析评估Rcl1过表达或敲低对细胞生长和转移的影响。

结果

RCL1表达在HCC中普遍下调。RCL1表达降低与更高的肿瘤分期、更高的甲胎蛋白(AFP)水平、血管侵犯和不良预后相关。RCL1表达与HCC中的免疫细胞浸润显著相关,尤其是髓系来源的抑制细胞(MDSC)。此外,进一步确定Rcl1表达在HCC细胞系中降低,并且与HCC细胞系的侵袭呈负相关。免疫荧光(IF)分析显示,HCC细胞胞质中Rcl1表达水平明显低于L-02细胞胞质中的水平。此外,功能获得和功能丧失研究均表明,Rcl1在体外抑制HCC细胞的生长和转移并调节细胞周期进程。

结论

Rcl1可能是HCC中的一种新型肿瘤抑制因子,其生物学效应有待进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3fc/8905783/5a885fbf56ca/12935_2022_2533_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3fc/8905783/9c5594efbcaa/12935_2022_2533_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d3fc/8905783/5a885fbf56ca/12935_2022_2533_Fig9_HTML.jpg

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本文引用的文献

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Nucleic Acids Res. 2021 Jun 4;49(10):5743-5759. doi: 10.1093/nar/gkab381.
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RCL1 copy number variants are associated with a range of neuropsychiatric phenotypes.RCL1 拷贝数变异与一系列神经精神表型相关。
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