| Shengnan Zhao,Aixia Chen,Jingyu Cao,Zusen Wang,Weiyu Hu,Fei Zhou,Donghai Liang,Hongsheng Yu. Neurotrophin 3 hinders the growth and metastasis of hepatocellular carcinoma cells*. Oncol Transl Med, 2020, 6: 143-152. |
| NTF3可以阻遏肝癌细胞的生长和转移 |
| Neurotrophin 3 hinders the growth and metastasis of hepatocellular carcinoma cells* |
| Received:May 08, 2020 Revised:May 08, 2020 |
| DOI：10.1007/s10330-020-0426-6 |
| 中文关键词: 肝细胞癌；肿瘤进展；NTF3 |
| 英文关键词: Hepatocellular carcinoma;Tumor progression;NTF3 |
| 基金项目: |
| Author Name | Affiliation | E-mail | | Shengnan Zhao | Department of Radiation Oncology, the Affiliated Hospital of Qingdao University, Qingdao 266000, China | zsn0613@163.com | | Aixia Chen | Department of Radiation Oncology, the Affiliated Hospital of Qingdao University, Qingdao 266000, China | | | Jingyu Cao | Department of Hepatobilary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Qingdao 266000, China | | | Zusen Wang | Department of Hepatobilary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Qingdao 266000, China | | | Weiyu Hu | Department of Hepatobilary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Qingdao 266000, China | | | Fei Zhou | Department of Hepatobilary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Qingdao 266000, China | | | Donghai Liang | Department of Radiation Oncology, the Affiliated Hospital of Qingdao University, Qingdao 266000, China | | | Hongsheng Yu* | Department of Radiation Oncology, the Affiliated Hospital of Qingdao University, Qingdao 266000, China | qdhsyu@126.com |
|
| Hits: 8770 |
| Download times: 9926 |
| 中文摘要: |
| 目的：神经营养蛋白3（Neurotrophin 3，NTF3）参与许多生物学过程，尤其是参与神经元细胞的存活与分化。但是，其在实体肿瘤中的研究内容不多，目前尚未报道其在肝细胞癌（Hepatocellular carcinoma，HCC）中的作用。随着生物信息技术的不断更新完善，这项研究通过大数据分析得到NTF3在肝癌中的表达量以及生存预后。对NTF3设置不同的表达水平进行体外实验，研究NTF3在HCC进展中的功能，并揭示了其潜在的分子机制。
方法：通过对公开获得的The Cancer Genome Atlas（TCGA）数据库进行生物信息学分析，挖掘NTF3在肝癌组织及与其对应的癌旁组织中的表达量及预后相关性。取部分临床标本使用实时定量PCR（Quantitative real time polymerase chain reaction，qRT-PCR)检测用于验证NTF3在肝癌中的表达水平，同时将HCC组织的石蜡标本进行免疫组织化学研究（immunohistochemistry,IHC）以观察NTF3的表达量。通过细胞计数试剂盒（Cell Counting Kit-8，CCK-8）对细胞的生长和增殖进行分析。细胞的侵袭和迁移通过Transwell小室和伤口愈合测定法（Wound Healing）进行分析。通过免疫印迹实验（Western Blot）和qRT-PCR检测（n=80）以评估蛋白质表达量和mRNA水平。通过流式细胞术评估细胞凋亡。
结果：TCGA数据库显示与邻近的非肝癌组织（adjacent nontumorous liver tissue,ANLT）相比NTF3在肝癌组织中显著下调，差异具有统计学意义（P＜0.001）。 而NTF3的较低表达与患者总体生存期降低明显相关，qRT-PCR和IHC结果显示HCC组织中NTF3的表达总体较低。NTF3过表达减少了HCC细胞系的增殖，迁移和侵袭。NTF3的较低表达与临床病理特征有明显相关性。
结论：根据TCGA数据库分析以及临床样本验证均表明，NTF3在肝癌组织中的表达量较低，而低表达NTF3可以通过促进HCC细胞增殖、迁移和侵袭而参与HCC患者的不良预后。我们的发现为HCC的发病机理和NTF3在肿瘤进展中的作用提供了新的认识，表明靶向NTF3对于HCC治疗具有潜在的治疗和诊断价值。并且为以后的研究提供了实验基础。 |
| 英文摘要: |
| Objective: Neurotrophin 3 (NTF3) is involved in numerous biological processes; however, its role in hepatocellular carcinoma (HCC) is not well examined. This study investigated NTF3 function in HCC progression and revealed the underlying molecular mechanisms. Methods: The prognostic relevance of NTF3 was determined by bioinformatical analysis of publicly available TCGA data. Immunohistochemistry of HCC biopsies were performed for exploring the expression of NTF3. Cell growth and proliferation were analyzed by Cell Counting Kit-8 (CCK-8) assay. Cell invasion and migration were analyzed by Boyden transwell and wound healing assays. Protein expression and mRNA levels were evaluated by immunoblotting and quantitative polymerase chain reaction (qPCR). Cell apoptosis was evaluated by flow cytometry. Results: NTF3 expression was overall lower in HCC tissues compared to adjacent non-tumor tissues. Lower NTF3 expression was significantly associated with decreased patient overall survival and lower NTF3 expression was significantly associated with clinicopathological features. NTF3 overexpression reduced the proliferation, migration, and invasion of HCC cell lines. Conclusions: Decreased expression of NTF3 is involved in poor prognosis of patients with HCC by promoting HCC cell proliferation, migration, and invasion. Our findings provided novel understanding into the pathogenesis of HCC and the role of NTF3 in tumor progression, suggesting that targeting NTF3 has potential therapeutic and diagnostic value for HCC treatment. |
|
View Full Text
Download reader HTML全文 |
| Close |
|
|
|