PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway.
PRC1 contributes to tumorigenesis of lung adenocarcinoma in association with the Wnt/β-catenin signaling pathway.
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PRC1 与 Wnt/β-catenin 信号通路相关，有助于肺腺癌的肿瘤发生
DOI：
10.1186/s12943-017-0682-z
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发表时间：
2017-06-24
期刊：
影响因子：
37.3
通讯作者：
Song Y
中科院分区：
文献类型：
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作者：
Zhan P;Zhang B;Xi GM;Wu Y;Liu HB;Liu YF;Xu WJ;Zhu QQ;Cai F;Zhou ZJ;Miu YY;Wang XX;Jin JJ;Li Q;Qian LP;Lv TF;Song Y
胞质分裂调节蛋白-1(Protein Reguler of Cytokinesis-1，PRC1)属于微管相关蛋白(MAPs)家族，参与胞质分裂。近年来的研究表明，PRC1参与了乳腺癌、肝细胞癌等人类的癌变过程，但其是否参与肺腺癌的发生尚不清楚。方法采用定量逆转录聚合酶链式反应(qRT-PCR)、Western blotting和免疫组织化学染色(IHC)方法检测和对比肺腺癌及癌旁正常肺组织中PRC1的表达情况。我们研究了PRC1在肺腺癌预后中的临床应用。此外，通过体外和体内转移和成瘤实验验证了PRC1对肺腺癌细胞的成瘤作用。结果肺腺癌组织中PRC1mRNA和蛋白的表达均较癌旁正常肺组织表达上调。PRC1蛋白过度表达与肺腺癌患者的淋巴转移有关，是肺腺癌患者预后不良的独立因素。我们的研究结果提示，Prc1缺失在体外抑制了肺腺癌细胞的增殖和侵袭，并降低了体内肿瘤的发展和肺转移。值得注意的是，限制PRC1显著促进了G2/M期细胞周期停滞和细胞凋亡。从机制上讲，通过对缺失Prc1的A549细胞和对照细胞进行NGS，我们发现Prc1的表达与Wnt信号通路密切相关。结论本研究证实了Prc1是肺腺癌患者预后和有前景的治疗生物标志物，并在肺腺癌发生过程中Wnt/β-catenin通路的激活中起着关键作用。
BackgroundProtein regulator of cytokinesis-1 (PRC1) belongs to the microtubule-associated proteins (MAPs) family, and is involved in cytokinesis. Recent investigations suggest PRC1 involvement in human carcinogenesis, including breast carcinoma, hepatocellular carcinoma and etc. However, whether PRC1 contributes to lung adenocarcinoma tumorigenesis remains unknown.MethodsQuantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blotting and Immunohistochemical staining (IHC) were used to evaluate and contrast the PRC1 expression profile in lung adenocarcinoma and adjacent normal lung tissues. We examined the clinical use of PRC1 in lung adenocarcinoma prognosis. Additionally, the tumorigenesis impact of PRC1 in lung adenocarcinoma cells was verified via in vitro and in vivo metastasis and tumorigenesis assays. Notably, Next Generation Sequencing (NGS) was performed to investigate the molecular mechanism underlying the oncogenic role of PRC1 in lung adenocarcinoma.ResultsPRC1 mRNA and protein expressions were upregulated in lung adenocarcinoma tissues compared to adjacent normal lung tissues. PRC1 protein overexpression correlated with lymph node metastasis and was an independent poor prognostic factor for lung adenocarcinoma patients. Our data implied that PRC1 depletion limited the proliferation and invasion of lung adenocarcinoma cells in vitro and lowered tumor development and lung metastasis in vivo. Remarkably, limiting PRC1 substantially prompted G2/M phase cell cycle arrest and apoptosis. Mechanistically, by conducting NGS on PRC1-depleted A549 cells and control cells, we discovered that PRC1 expression was significantly correlated with the Wnt signaling pathway.ConclusionsThis investigation offers confirmation that PRC1 is a prognostic and promising therapeutic biomarker for people with lung adenocarcinoma and takes on a key part in the activation of the Wnt/β-catenin pathway in lung adenocarcinoma development.