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Obg-like ATPase 1 (OLA1) 过表达通过调节肝细胞癌中的 P21/CDK2 促进肿瘤进展,预测不良预后。

Obg-like ATPase 1 (OLA1) overexpression predicts poor prognosis and promotes tumor progression by regulating P21/CDK2 in hepatocellular carcinoma.

机构信息

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou 510080, China.

Organ Transplant Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.

出版信息

Aging (Albany NY). 2020 Feb 11;12(3):3025-3041. doi: 10.18632/aging.102797.

Abstract

BACKGROUND

Obg-like ATPase 1 (OLA1) has been found to have a dual role in cancers. However, the relationship between OLA1 and hepatocellular carcinoma (HCC) remains unclear.

RESULTS

High expression of OLA1 in HCC was detected in public datasets and clinical samples, and correlated with poor prognosis. Downregulation of OLA1 significantly inhibited the proliferation, migration, invasion and tumorigenicity of HCC cells. Mechanistically, GSEA showed that OLA1 might promote tumor progression by regulating the cell cycle and apoptosis. In addition, OLA1 knockdown resulted in G0/G1 phase arrest and high levels of apoptosis. OLA1 could bind with P21 and upregulate CDK2 expression to promote HCC progression.

CONCLUSIONS

Overall, these findings uncover a role for OLA1 in regulating the proliferation and apoptosis of HCC cells.

MATERIALS AND METHODS

The Cancer Genome Atlas and Gene Expression Omnibus datasets were analyzed to identify gene expression. Immunohistochemistry staining, western blot and real-time polymerase chain reaction were performed to evaluate OLA1 expression in samples. Cell count Kit-8, wound-healing, transwell and flow cytometry assays were used to analyze HCC cell progression. Subcutaneous xenotransplantation models were used to investigate the role of OLA1 in vivo. Coimmunoprecipitation was used to analyze protein interactions.

摘要

背景

Obg-like ATPase 1(OLA1)在癌症中具有双重作用。然而,OLA1 与肝细胞癌(HCC)之间的关系尚不清楚。

结果

公共数据集和临床样本中检测到 HCC 中 OLA1 的高表达,并与预后不良相关。OLA1 的下调显著抑制 HCC 细胞的增殖、迁移、侵袭和致瘤性。机制上,GSEA 表明 OLA1 可能通过调节细胞周期和细胞凋亡来促进肿瘤进展。此外,OLA1 下调导致 G0/G1 期阻滞和高水平凋亡。OLA1 可以与 P21 结合并上调 CDK2 表达以促进 HCC 进展。

结论

总的来说,这些发现揭示了 OLA1 在调节 HCC 细胞增殖和凋亡中的作用。

材料和方法

分析癌症基因组图谱和基因表达综合数据库数据集以鉴定基因表达。免疫组织化学染色、Western blot 和实时聚合酶链反应用于评估样本中 OLA1 的表达。细胞计数试剂盒-8、划痕愈合、Transwell 和流式细胞术分析用于分析 HCC 细胞进展。皮下异种移植模型用于体内研究 OLA1 的作用。免疫共沉淀用于分析蛋白质相互作用。

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