The Relationship Between CELF1、ENTPD5 And Lung Cancer

Lung cancer is one of the leading causes of cancer related deaths worldwide. Studies have shown that the genes and target proteins involved in lung cancer function in cell proliferation, apoptosis, and angiogenesis pathways. Identifying a mechanism that inhibits the growth of lung cancer cells would be useful in developing potential treatments for lung cancer.The CELF(CUGBP and Etr-like factors) family proteins are major sequence-specific RNA binding proteins that control alternative splicing and mRNA translation and stability. Some reports have demonstrated that CELF1 protein regulates pre-mRNA alternative splicing and is involved in mRNA editing and translation. Ectonucleoside triphosphate diphosphohydrolase 5(ENTPD5) is a kind of enzyme in the endoplasmic reticulum that hydrolyzes to UMP to promote protein N-glycosylation and folding in the endoplasmic reticulum. ENTPD5 protein is distinctive from other NTPDases as it is the only member that is described as a proto-onco protein.Whether the expression of the CELF1 gene and ENTPD5 gene are related to the proliferation of human lung cancer has not been investigated.In this study, we used the molecular biology technique to explore the relationship between the CELF1, ENTPD5 and the prognosis of lung cancer patient.We finished the following works:1.Here we investigated the relationship between CELF1 expression and lung cancer clinicopathological factors at the RNA level and clarified the physiological impact of CELF1 on lung cancer cell growth at the cellular level. The expression of CELF1 was higher in human lung cancer tissues compared with the normal lung tissue.Lentiviral-mediated transfection of CELF1 siRNA effectively silenced the expression of CELF1 in both A549 and H1299 cells. Moreover, CELF1 knockdown markedly reduced the survival rate of lung cancer cells. Colony formation assays revealed a reduction in the number and size of lung cancer cell colonies from CELF1 knockdown.2. This study is to investigate the relationship between ectonucleoside triphosphate diphosphohydrolase 5(ENTPD5) expression and lung cancer clinicopathological factors, and the impact of ENTPD5 on lung cancer cell functions. Lung cancer specimens and matched adjacent normal tissues were obtained from patients without any preoperative radiotherapy or chemotherapy. Knockdown of ETNPD5 expression led to significantly decreased lung cancer cell growth rate, markedly increased apoptosis and the ability to repair, and significantly reduced invasion. Gene chip tests showed that knockdown of ENTPD5 expression caused more Caspase expression. Quantitative real-time polymerase chain reaction showed that the Caspase 3 expression was significantly increased after the knockdown of ENTPD5. In addition, immunohistochemistry showed that the tumor growth marker, proliferating cell nuclear antigen, was significantly reduced in the knockdown model. Tumorigenicity assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay showed that the apoptosis of lung cancer cells was increased in the knockdown model. Our results suggest that ENTPD5 affects lung cancer apoptosis via Caspase 3 pathway, and can be potentially used to monitor prognosis or to guide appropriate therapeutic regimens.In conclusion, this study explained the relationship between lung cancer and CELF1, ENTPD5, iASPP, find the associated signaling pathways, produced a certain practical significance.