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下调通过细胞周期蛋白4依赖性激酶-1/信号转导和转录激活因子3途径介导的机制促进侵袭性肝细胞癌。

Downregulation Contributes to Aggressive Hepatocellular Carcinoma via Mechanism Mediated by Cyclin4-Dependent Kinase-1/STAT3 Pathway.

作者信息

Shen Ying, Li Xin, Su Yanwei, Badshah Shaikh Atik, Zhang Bin, Xue Yanru, Shang Peng

机构信息

Research & Development Institute of Northwestern Polytechnical University in Shenzhen, Shenzhen 518057, China.

School of Life Science, Northwestern Polytechnical University, Xi'an 710072, China.

出版信息

Diagnostics (Basel). 2019 Apr 30;9(2):48. doi: 10.3390/diagnostics9020048.

DOI:10.3390/diagnostics9020048
PMID:31052210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6628061/
Abstract

BACKGROUND

Hepcidin encoded by is vital to regulating proliferation, metastasis, and migration. Hepcidin is secreted specifically by the liver. This study sought to examine the functional role of hepcidin in hepatocellular carcinoma (HCC).

METHODS

Data in the Cancer Genome Atlas database was used to analyze expression as it relates to HCC prognosis. We then used the 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, transwell assay, and flow cytometric analysis, respectively, to assess proliferation, migration, and the cell cycle. Gene set enrichment analysis (GSEA) was used to find pathways affected by .

RESULTS

expression was lower in hepatocellular carcinoma samples compared with adjacent normal tissue controls. Low expression was linked with a higher rate of metastasis and poor disease-free status. Downregulation of induced SMMC-7721 and HepG-2 cell proliferation and promoted their migration. could affect the cell cycle pathway and Western blotting, confirming that reduced levels activated cyclin-dependent kinase-1/stat 3 pathway.

CONCLUSION

Our findings indicate that functions as a tumor suppressor gene. The role of in cellular proliferation and metastasis is related to cell cycle checkpoints. could be considered as a diagnostic biomarker and targeted therapy in HCC.

摘要

背景

由[基因名称]编码的铁调素对于调节细胞增殖、转移和迁移至关重要。铁调素由肝脏特异性分泌。本研究旨在探讨铁调素在肝细胞癌(HCC)中的功能作用。

方法

利用癌症基因组图谱数据库中的数据来分析[基因名称]表达与HCC预后的关系。然后我们分别使用5-乙炔基-2'-脱氧尿苷(EdU)掺入试验、Transwell试验和流式细胞术分析来评估增殖、迁移和细胞周期。基因集富集分析(GSEA)用于寻找受[基因名称]影响的通路。

结果

与相邻正常组织对照相比,肝细胞癌样本中[基因名称]表达较低。低[基因名称]表达与较高的转移率和较差的无病状态相关。[基因名称]的下调诱导了SMMC-7721和HepG-2细胞增殖并促进了它们的迁移。[基因名称]可影响细胞周期通路并通过蛋白质印迹法得到证实,即[基因名称]水平降低激活了细胞周期蛋白依赖性激酶-1/信号转导和转录激活因子3通路。

结论

我们的研究结果表明[基因名称]作为一种肿瘤抑制基因发挥作用。[基因名称]在细胞增殖和转移中的作用与细胞周期检查点有关。[基因名称]可被视为HCC的诊断生物标志物和靶向治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f3/6628061/23b08a88c8ec/diagnostics-09-00048-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f3/6628061/23b08a88c8ec/diagnostics-09-00048-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/52f3/6628061/23b08a88c8ec/diagnostics-09-00048-g002.jpg

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