Ring finger protein 38 promote non-small cell lung cancer progression by endowing cell EMT phenotype.
Ring finger protein 38 promote non-small cell lung cancer progression by endowing cell EMT phenotype.
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无名指蛋白38通过赋予细胞EMT表型促进非小细胞肺癌进展
DOI：
10.7150/jca.23138
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发表时间：
2018
影响因子：
3.9
通讯作者：
Ding JY
中科院分区：
文献类型：
--
作者：
Xiong D;Zhu SQ;Wu YB;Jin C;Jiang JH;Liao YF;Long X;Wu HB;Xu JJ;Li JJ;Ding JY
目的：环指蛋白38（Ring finger protein 38，RNF 38）是一种E3泛素连接酶，位于第9号染色体（9 p13）上，参与包括肺癌在内的多种肿瘤的发生发展，通过调控细胞凋亡、细胞周期和DNA修复等多种生物学过程发挥重要作用。然而，其在肿瘤发生中的功能仍不清楚。因此，本研究旨在探讨RNF 38在非小细胞肺癌（NSCLC）中的生物学功能和临床意义。材料和方法：采用免疫组化、实时定量聚合酶链反应（qRT-PCR）和western blot方法检测NSCLC及相应癌旁组织中RNF 38蛋白和mRNA的表达。应用组织芯片技术分析208例NSCLC组织中RNF 38的表达与临床意义的关系。Kaplan-Meier分析和log-rank检验评估预后价值。分别采用伤口愈合实验、trans-well实验、集落形成实验和CCK 8检测细胞的迁移、侵袭和增殖能力。通过免疫荧光和蛋白质印迹分析上皮向间充质转化（EMT）表型。结果如下：RNF 38在NSCLC组织中的表达水平高于配对正常组织，mRNA水平（2.82 ± 0.29 vs.1.23 ± 0.13）和蛋白水平（2.75 ± 0.09 vs.1.24 ± 0.02）均高于配对正常组织。RNF 38的高表达水平与淋巴结转移、较高的TNM分期（p=0.011）、较大的肿瘤大小（p=2.09E-04）显著相关，并预测不良预后。RNF 38表达与E-cadherin表达呈负相关（P= 0.025）。此外，RNF 38的下调损害了NSCLC细胞的增殖、转移和侵袭能力。此外，RNF 38的异常表达可调节EMT的关键分子。结论：我们的研究结果表明，RNF 38的高表达与NSCLC细胞的增殖和转移能力显著相关，RNF 38过表达可作为NSCLC预后不良的生物标志物。
Objectives: Ring finger protein 38 (RNF38), as an E3 ubiquitin ligase, plays an essential role in multiple biological processes by controlling cell apoptosis, cell cycle and DNA repair, and resides in chromosome 9 (9p13) which is involvement in cancer pathogenesis including lung cancer. However, its function in tumorigenesis remains unclear. Hence, this study set out to investigate the biological function and clinical implications of RNF38 in non-small cell lung cancer (NSCLC). Materials and Methods: Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to detect RNF38 protein and mRNA levels in NSCLC and corresponding paratumor tissues. Tissue microarrays (TMA) analysis of 208 NSCLC cases were used to evaluate the relationship between RNF38 expression and clinical implications. Prognostic value was assessed by Kaplan-Meier analysis and log-rank tests. Wound-healing assays, trans-well assays, colony formation assays and CCK8 were used to assess cell migration, invasion and proliferative ability respectively. The analysis of epithelial-to-mesenchymal transition (EMT) phenotype was carried out by immunofluorescence and western blot. Results: Our data revealed that elevated RNF38 expression were more common in NSCLC tissues than paired normal tissues in both mRNA (2.82 ± 0.29 vs. 1.23 ± 0.13) and protein (2.75 ± 0.09 vs. 1.24 ± 0.02) level. High levels of RNF38 expression were significantly associated with lymph node metastases, higher TNM stages (p=0.011), larger tumor size (p=2.09E-04) and predicted poor prognosis. RNF38 expression was inversely correlated with E-cadherin expression (P= 0.025). Moreover, downregulation of RNF38 impaired the proliferation, metastatic and invasive abilities in NSCLC cells. In addition, aberrant RNF38 expression could modulate the key molecules of EMT. Conclusions: Our results indicate that elevated expression of RNF38 is significantly associated with the proliferation and metastatic capacity of NSCLC cells, and RNF38 overexpression can serve as a biomarker of NSCLC poor prognosis.
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DOI：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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