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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Carcinoma, Squamous Cell / genetics
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Carcinoma, Squamous Cell / metabolism*
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Cell Cycle / genetics
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Cell Cycle / physiology*
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Cell Cycle Checkpoints / genetics
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Cell Cycle Checkpoints / physiology
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Cell Line, Tumor
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Esophageal Neoplasms / genetics
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Esophageal Neoplasms / metabolism*
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Esophageal Squamous Cell Carcinoma
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Humans
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Immunohistochemistry
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In Vitro Techniques
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Nude
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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RNA Interference
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Retinoblastoma Protein / genetics
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Retinoblastoma Protein / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Tissue Array Analysis
Substances
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CDKN1A protein, human
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CRNN protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Membrane Proteins
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Neoplasm Proteins
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Retinoblastoma Protein
Grants and funding
This work was supported by Grants from the National Natural Science Foundation of China (81272416, 81172338 and 81000863); the General Research Fund (HKU 7668/11M); Sun Yat-Sen University “Hundred Talents Program” (85000-3171311) and Sun Yat-sen University Young Talent Teachers Plan (11ykpy58). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.