RUFY3 Predicts Poor Prognosis and Promotes Metastasis through Epithelial-mesenchymal Transition in Lung Adenocarcinoma
RUFY3 Predicts Poor Prognosis and Promotes Metastasis through Epithelial-mesenchymal Transition in Lung Adenocarcinoma
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DOI：
10.7150/jca.35072
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Gong, Shulei
中科院分区：
文献类型：
--
作者：
Men, Wanfu;Li, Wenya;Gong, Shulei
背景：RUFY3 （RUN和FYVE结构域蛋白3）已被证明参与细胞迁移、膜运输和细胞信号传导，并在几种癌症过程中失调。然而，RUFY3在肺癌中的作用尚不清楚。在本研究中，我们旨在研究RUFY3在肺腺癌中的表达，并评估其临床意义。材料与方法：采用免疫组化方法检测125例肺癌手术切除的人肺腺癌及邻近正常肺组织中RUFY3蛋白的表达。评估RUFY3表达与肺腺癌患者临床病理特征及临床预后的关系。western blot检测3种不同肺腺癌细胞系和1种正常肺上皮细胞（BEAS-2B）中RUFY3的表达。采用RNAi技术沉默RUFY3。我们通过Trans-well实验和伤口愈合实验评估细胞迁移。结果：在肺腺癌组织中，RUFY3蛋白较配对的正常肺组织显著上调。高细胞质RUFY3水平与淋巴结转移、TNM分期和生存状态相关。RUFY3表达水平最高的患者比表达水平最低的患者生存时间短。siRNA抑制RUFY3可抑制细胞迁移。RUFY3的沉默导致E-cadherin表达上调，而N-cadherin、Vimentin和Slug表达下调。结论：我们的研究首次证实了RUFY3在肺腺癌中的异常表达预示着预后不良，也提示了RUFY3可能与EMT过程有关。这凸显了RUFY3作为肺腺癌新的预后生物标志物的潜力。
Background: RUFY3 (RUN and FYVE domain-containing protein 3) has been shown to participate in cell migration, membrane transportation, and cellular signaling and is dysregulated in several cancer processes. However, the role of RUFY3 in lung cancer remains unclear. In the present study, we aimed to study the expression of RUFY3 and assess its clinical significance in lung adenocarcinoma.Materials and Methods: We used immunohistochemistry to detect RUFY3 protein expression in human lung adenocarcinoma and adjacent normal lung tissue from 125 patients who underwent surgical resection of the lung cancer. RUFY3 expression was assessed in association with clinicopathological characteristics and clinical prognosis of lung adenocarcinoma patients. The expression of RUFY3 in three different lung adenocarcinoma cell lines and one normal lung epithelial cell (BEAS-2B) was detected by western blot. RNAi technique was used to silence RUFY3. We assessed cell migration by Trans-well assay and wound healing assay.Results: In lung adenocarcinoma tissues, RUFY3 protein was significantly upregulated compared to paired normal lung tissues. High cytoplasmic RUFY3 levels were associated with lymph node metastasis, TNM staging, and survival status. Patients with the highest expression level of RUFY3 had a shorter survival time than patients with the lowest expression. Inhibition of RUFY3 by siRNA inhibited cell migration. Furthermore, silence of RUFY3 lead to up-regulation of E-cadherin, but down-regulation of N-cadherin, Vimentin and Slug.Conclusions: Our study is first to demonstrated that abnormal expression of RUFY3 indicates poor prognosis in lung adenocarcinoma and also indicates that RUFY3 may be related to EMT process. This highlights the potential of RUFY3 as a novel prognostic biomarker for lung adenocarcinoma.