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LOH12CR1 is a Novel Tumor Suppressor Inhibiting Tumor Growth Through Deregulation of G1/S Checkpoint in Human Colorectal Carcinoma

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Background: Loss of heterozygosity (LOH) of 12p12-13 has been frequently found in various types of cancer. LOH12CR1 is one of the seven critical genes located within the 12p12-13 region. The protein encoded by LOH12CR1 is involved in the function of lysosomes and its other functions are still unclear.

Objective: The aim of this study is to investigate the potential roles of LOH12CR1 in the development of colorectal cancer.

Methods: A total of 174 colorectal cancer tissues were used to examine the protein level of LOH12CR1 by immunohistochemistry staining. The correlation between LOH12CR1 expression and the patient prognosis was further investigated through retrospective study. The tumor suppression capacity was examined by knockdown or overexpression of LOH12CR1 in four colorectal cancer cell lines and one normal cell line.

Results: Significant decrease of LOH12CR1 protein was observed in colorectal cancerous tissues (P<0.001). Knockdown of LOH12CR1 promoted colorectal cancer cell proliferation, colony formation, and accelerated G1/S cell cycle transition through downregulation of p16INK4a and p21WAF1/CIP1, while ectopic expression of LOH12CR1 displayed the opposite effects. The protein level of LOH12CR1 was well correlated with the expression of p16INK4a and p21WAF1/CIP1. Most importantly, the protein level of LOH12CR1 negatively correlated with clinical prognosis of colorectal carcinomas.

Conclusion: The present results suggest that LOH12CR1 might function as a tumor suppressor. Thus, loss of function of LOH12CR1 might be a potential driver in the development of colorectal carcinoma. Detection of LOH12CR1 could be used as a method for diagnosis and therapeutic assessment of patients with colorectal cancer.
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Keywords: G1/S arrest; LOH12CR1; cell cycle; colorectal cancer; p16; p21; tumor suppressor

Document Type: Research Article

Publication date: January 1, 2018

This article was made available online on June 14, 2018 as a Fast Track article with title: "LOH12CR1 is a Novel Tumor Suppressor Inhibiting Tumor Growth Through Deregulation of G1/S Checkpoint in Human Colorectal Carcinoma".

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  • Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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