Characterization of tumor suppressive function of cornulin in esophageal squamous cell carcinoma.

Characterization of tumor suppressive function of cornulin in esophageal squamous cell carcinoma.
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Cornulin在食管鳞癌中抑癌作用的表征

DOI:
10.1371/journal.pone.0068838
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Guan XY
Guan XY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen K;Li Y;Dai Y;Li J;Qin Y;Zhu Y;Zeng T;Ban X;Fu L;Guan XY

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通过基因芯片分析,我们发现cornulin(CRNN)基因在食管鳞状细胞癌(ESCC)中频繁下调。在本研究中,我们研究了CRNN在ESCC发展中的作用。结果显示,CRNN在mRNA水平(26/56,46.4%)和蛋白水平(137/249,55%)均在原发性食管鳞癌中表达下调,且与淋巴结转移(P = 0.027)、临床分期(P = 0.039)和总生存率(P <0.001)显著相关。多因素分析显示CRNN下调是食管鳞癌的独立预后因素。体外和体内功能研究表明,CRNN对ESCC细胞具有较强的肿瘤抑制能力。CRNN的抑瘤机制可能与其通过上调P21WAF 1/CIP1和Rb的表达,使细胞周期阻滞在G1/S关卡有关。利用RNA干扰技术沉默CRNN的表达可有效抑制其抑瘤作用。总之,我们的研究结果表明,CRNN是一个肿瘤抑制基因,在ESCC中起着关键的肿瘤抑制作用。
By using cDNA microarray analysis, we identified cornulin (CRNN) gene was frequently downregulated in esophageal squamous cell carcinoma (ESCC). In the present study, we investigated the role of CRNN in ESCC development. The results showed that CRNN was frequently downregulated in primary ESCCs in both mRNA level (26/56, 46.4%) and protein level (137/249, 55%), which was significantly associated with lymph node metastases (P=0.027), advanced clinical stage (P=0.039), and overall survival rate (P<0.001). Multivariate analysis indicated that the CRNN downregulation was an independent prognostic factor for ESCC. Functional studies with both in vitro and in vivo assays demonstrated that CRNN had strong tumor suppressive ability in ESCC cells. The tumor-suppressive mechanism of CRNN was associated with its role in cell cycle arrest at G1/S checkpoint by upregulating expressions of P21WAF1/CIP1 and Rb. Silencing CRNN expression by RNA interference could effectively inhibit its tumor suppressive effect. In conclusion, our findings demonstrate that CRNN is a tumor suppressor gene that plays a critical tumor suppressive role in ESCC.
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