title: Characterization of tumor suppressive function of cornulin in esophageal squamous cell carcinoma.
abstract: 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 P21(WAF1/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.
authors.affiliation: State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Yongdong
authors.initials: Y
authors.lastname: Dai
authors.forename: Jiangchao
authors.initials: J
authors.lastname: Li
authors.forename: Yanru
authors.initials: Y
authors.lastname: Qin
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Zhu
authors.forename: Tingting
authors.initials: T
authors.lastname: Zeng
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Ban
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Guan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D059447:Cell Cycle Checkpoints / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D000077277:Esophageal Squamous Cell Carcinoma; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046888:Tissue Array Analysis
chemical_list: C493956:CDKN1A protein, human; C418764:CRNN protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein
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