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
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.