The Roles Of NudC In Gastric Carcinogenesis

Gastric cancer is a serious threat to our health. The incidence of gastric cancer is about 680 thousand and the mortality is about 500 thousand per year in China. Although there are a lot of research progress about gastric cancer, the overall situation of gastric cancer in China is still high incidence, low early diagnosis rate and low five years survival rate. In order to improve the diagnosis, treatment of gastric cancer, it is necessary to carry out deep and systematic molecular biology research of gastric cancer.Nuclear distribution genes (Nud) were first found in Aspergillus nidulans to act as components or regulators of the cytoplasmic dynein complex. NudF, whose mammalian homologue is Lissencephaly 1 (Lisl), is an upstream regulatory factor of cytoplasmic dynein. Mutation of Lisl causes type I lissencenphaly Nuclear distribution gene C (NudC) regulates the stability of the LIS1. Recently, studies show that NudC plays important roles in cell cycle, cell migration, ciliogenesis, thrombopoiesis and inflammatory response. Meanwhile, NudC is also reported to be differentially expressed in cancers. However, the relationship between NudC and gastric cancer remains largely unknown.To study the role of NudC in the development of gastric cancer, we first analyze the correlation between NudC mRNA expression level of gastric cancer patients and their pathological information in TCGA database. Then we collect clinical gastric cancer patients’tissue samples and analyze NudC mRNA and protein expression level in these samples. We find that there is no significant expression difference of NudC mRNA in gastric cancer tissues. However, NudC protein level is markedly higher in gastric cancer tissues. Patients with high NudC protein level show low five years survival rate and obvious lymph node metastasis. In order to further study the mechanism, we down regulate the protein level of NudC in gastric cancer cell line BGC. Depletion of NudC inhibits BGC cell proliferation, migration and invasion. Since NudC acts as a cochaperone of Hsp90 and Hsp90 is related to tumorigenesis, we further explore the correlation between NudC and Hsp90 in gastric cancer. We find the expression of Hsp90 in gastric cancer tissue is higher. Meanwhile, the expression of NudC and Hsp90 show positive correlation.According to these data, NudC protein expression level is markedly higher in gastric cancer tissues and is associated with patients’ five years survival rate. NudC may be involved in proliferation, migration and invasion of gastric cancer cells through Hsp90 pathway. This study will be helpful to identify potential molecular marker for the diagnosis and prognosis of gastric cancer.