Downregulation of TRIM21 contributes to hepatocellular carcinoma carcinogenesis and indicates poor prognosis of cancers
Downregulation of TRIM21 contributes to hepatocellular carcinoma carcinogenesis and indicates poor prognosis of cancers
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TRIM21的下调有助于肝细胞癌的癌变并表明癌症的不良预后
DOI：
10.1007/s13277-015-3572-2
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发表时间：
2015-11-01
期刊：
影响因子：
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通讯作者：
Yu, Honggang
中科院分区：
文献类型：
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作者：
Ding, Qianshan;He, Du;Yu, Honggang
本研究的目的是探讨TRIM 21在肝细胞癌中的临床意义和功能作用。我们通过免疫组化（IHC）染色验证了TRIM 21在肝癌样品中下调。我们还证明了它的下调与几个临床病理特征相关，如肿瘤数量，T分期，巴塞罗那临床肝癌（BCLC）分期和肝癌意大利计划（CLIP）分期。重要的是，TRIM 21在肿瘤样品中的表达与患者的预后显著相关。我们进一步沉默肝癌细胞HepG 2和LM 3中的TRIM 21，并证实TRIM 21沉默将促进癌细胞增殖（CCK-8测定）、集落形成（平板集落形成测定）、迁移（transwell测定）和抗凋亡能力（annexin V-FITC/PI染色）。然后，我们预测了受TRIM 21影响的基因集，通过使用生物信息学工具。我们首次证明了TRIM 21在HCC中是一个潜在的肿瘤抑制因子，其低表达提示预后不良。我们的研究结果为肝癌的起源和发展机制提供了有用的见解，并为新的肝癌治疗提供了线索。
The aim of our work is to clarify the clinical implication and functional role of tripartite motif 21 (TRIM21) in hepatocellular carcinoma (HCC). We validated that TRIM21 was downregulated in liver cancer samples by immunohistochemical (IHC) staining. We also demonstrated that its downregulation was associated with several clinicopathologic features such as tumor numbers, T stage, Barcelona Clinic Liver Cancer (BCLC) stage, and Cancer of the Liver Italian Program (CLIP) stage of HCC patients. Importantly, the expression of TRIM21 in tumor samples is significantly correlated with the prognosis of the patients. We further silenced TRIM21 in HCC cell HepG2 and LM3 and confirmed that TRIM21 silencing will promote cancer cell proliferation (CCK-8 assay), colony forming (plate colony-forming assay), migration (transwell assay), and the ability of antiapoptosis (annexin V-FITC/PI staining) in vitro. Then, we predicted gene sets influenced by TRIM21 by using bioinformatic tools. For the first time, we prove that TRIM21 is a potential tumor suppressor in HCC and its low expression indicates poor prognosis. Our findings provide useful insight into the mechanism of HCC origin and progression and offer clues to novel HCC therapies.