The Expression And Function Of HEG1 In Lung Cancer/the Alternative Splicing Variants Of Focal Adhesion Kinase In Pancreas Tumor

Heart development protein with epidermal growth factor-like domains 1 or protein HEG homolog 1(HEG1)is a mucin-like transmembrane protein that has been expressed in various tissues and plays important roles in angiogenesis,vascular integrity,embryonic development as well as tumor progression.In this study,the expression of HEG1 in cancers was analyzed in eight databases including 68 362 subjects with 33 cancers,and the findings were validated both in vitro and in vivo in lung cancer.We showed that HEG 1 was aberrantly expressed in 24 cancers,and its expression level was positively or negatively correlated with clinical outcome of 5 or 7 cancers,respectively.Mutations of HEG 1 were detected,and the mutations were distributed throughout the entire gene.Specifically,HEG1 was associated with tumor-infiltrating immune cells and was co-expressed with multiple immune checkpoints in patients with non-small cell lung cancer(NSCLC).Inspired by the above data,NSCLC was chosen to further investigate the HEG1 effects and molecular functions in tumor progression.Overexpression of HEG1 significantly inhibits the lung cancer cell proliferation and promotes cell apoptosis,while knockdown of HEG 1 enhances the cell proliferation and declines cell apoptosis in vitro and promotes the tumor growth in vivo.In addition,the HEG1 expression level is positively correlated to the apoptotic protein elevation,including NOXA,PUMA,BAK,BAX,and negatively correlated to anti-apoptotic protein BCL-2.Taken together,these results suggest HEG 1 may function as a tumor suppressor and may serve as a potential prognostic biomarker in NSCLC,providing a new idea for the treatment of lung cancer.Alternative splicing variants plays an important role in the progression and development of cancer,while the oncogene facal adhesive kinase(FAK)has been proven with a variety of alternative splicing variants.In particular,Box6/Box7-containing FAK variants(FAK6/7)is found with a high frequency in some cancers,including NSCLC.Characteristic genetic abnormality of neuroendocrine neoplasms(NENs),a heterogeneous group of tumors found in various organs,has rarely been identified.Here,by analyzing the splicing variants of FAK in The Cancer Genome Atlas(TCGA)datasets that contain 33 cancer subtypes,it showed that FAK6/7 were seen in 7(87.5%)of 8 pancreatic neuroendocrine carcinomas(PanNECs)and 20(11.76%)of 170 pancreatic ductal adenocarcinomas(PDACs).We tested FAK variants in 102 tumor samples collected from Chinese patients with pancreatic tumors,and found that FAK6/7 was positive in 12(44.44%)of 27 pancreatic solid pseudopapillary neoplasms,27(77.15%)of 35 pancreatic NENs(pNENs)and 2(5%)of 40 PDACs.These results suggested that FAK6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.