Pilot Study Of The GABARAPL1Gene Expression Changes In HCC Tissue

Hepatocellular carcinoma (HCC) is one of the ten malignant tumors defined by the World Health Organization. At present,400-500thousand people died of primary liver cancer in China annually and its mortality takes the third place in the digestive system tumors. However, there is no effective method for HCC treatment because of minor early symptoms, high degree of malignancy, and fast-speed of disease progression. In recent years, more and more studies demonstrate that abnormal autophagy is closely related to many diseases and malignant tumors. Therefore, the study of autophagy-related genes and cancer occurrence and development is of great importance for a comprehensive understanding of the mechanisms of liver cancer as well as the future prevention and treatment.GABARAPL1(GABA (A) receptor-associated protein like1) is one of the autophagy-related genes, first cloned and identified in our laboratory. By far, the study of this gene is still very limited, especially the role of the gene in the development of liver cancer has so far not been reported. Therefore, to explore GABARAPL1expression changes in hepatocellular carcinoma and its physiological function is indispensable for a comprehensive understanding of the mechanisms of liver cancer development.The mRNA expression of GABARAPL1was detected in104pairs of HCC tissue samples by real-time quantitative PCR taqman method and GABARAPL1mRNA was significantly lower in HCC than those in their adjacent nontumorous tissues. GABARAPL1down-expression was found to correlate significantly with the history of suffering from hepatitis type B, Hepatitis B Virus infection and survival time by pathological correlation analysis. Meanwhile, the protein expression of GABARAPL1was detected using specific antibody of anti-GABARAPL1in HCC tissue samples and GABARAPL1protein is also downregulated in cancer tissues than those in their adjacent nontumorous tissues.Then we proceeded to verify that a variety of liver cancer cell lines can express the endogenous GABARAPL1protein, which laid the foundation to select cell lines for later experiments. Moreover, stable cell strains with overexpression GABARAPL1were constructed in Hep3B cell lines, and further study showed that GABARAPL1overexpression significantly inhibited the proliferation of hepatoma cells by two experiment methods of growth curve and colony formation rate.In sum, we found a gene GABARAPL1, down regulated significantly in HCC. Further studies illustrated that the expression level of GABARAPL1had correlation with clinical pathological features and overexpression of GABARAPL1can inhibit hepatoma cell proliferation. Therefore, a succession of in-depth study of the molecular mechanisms of GABARAPL1in the development of liver cancer is of great significance for a new theoretical foundation for future prevention and treatment of liver cancer. The Human Genome Project was launched at the end of1980s. Since then, the cloning and identification of functional genes has been a major focus of research across the world. In China too, the potentially profound impact of such studies on the life sciences and on human health was realized, and relevant studies were initiated in the1990s. To advance China’s involvement in the Human Genome Project, in the mid-1990s, committee of Experts in Biology from National High Technology Research and Development Program of China (863Program) proposed the "two1%" goal.This goal envisaged China contributing1%of the total sequencing work, and cloning and identifying1%of the total human functional genes. Over the past20years, tremendous achievement has been accomplished by Chinese scientists. It is well known that scientists in China finished the1%of sequencing work of the Human Genome Project, whereas, there is no comprehensive report about "whether China had finished cloning and identifying1%of human functional genes:.In the present study, the GenBank database at the National Center of Biotechnology Information, the PubMed search tool, and the patent database of the State Intellectual Property Office, China, were used to retrieve entries based on two screening standards:1). were the newly cloned and identified genes first reported by Chinese scientists?; and2). were the Chinese scientists awarded the gene sequence patent? Entries were retrieved from the databases up to the cut-off date of30June2011and the obtained data were analyzed further. The results showed that589new human functional genes were first reported by Chinese scientists and159gene sequences were patented (http://gene.fudan.sh.cn/introduction/database/chinagene/chinagene.html). This study systematically summarizes China’s contributions to human functional genomics research and answers the question "has China finished cloning and identifying1%of human functional genes?" in the affirmative.