| Esophageal cancer is one of the most aggressive cancers. China, as a high incidence of esophageal cancer country, whose esophageal cancer histopatho logical form is mostly esophageal squamous cell carcinoma(ESCC) and with poor prognostic effect and low survival rate. For lack of favorable therapeutic method, gene therapy has become one of research hotspots. P53is an important tumor suppressor gene, which plays a vital significant role in controlling cell growth and inactivation. P53terms "Hallmarks of Cancer". In fact, it has been estimated that nearly50%of human cancers carry somatic mutations of the P53gene, mainly in DNA binding domain(DBD), which inactivate the normal function of P53. At present, many P53gene mutations have been found, which contained multiple "hot spot", and have been proved that they could either deprive P53tumor suppressor function or gain of oncogene function such as promoting cell proliferation, inducing angiogenesis, increasing drug resistance, promoting cell migration and invasion ability et al. According to the results of Genome Wide Association Study(GWAS), we found some new mutations in P53DBD from esophageal squamous carcinoma clinical samples. We focused on two mutations (p53G113C and p53R141H) with high rate and verified the oncogenicity. MTS, clone formation, flow cytometry technology, transwell assay were applied to test the influence on cell phenotype and we found that they could gain of oncogene function like promoting cell vitality, inhibiting cell apoptosis, weakening the P53mediating cell cycle arrest, promoting cell migration and invasion. So they both had cancer promoting functions.Eukaryotic3’untranslated regions (3’UTR) abnormal expression plays an important role in the processes of cell differentiation, growth and proliferation, apoptosis and development of tumor, which was gradually attracted by more and more researchers. Not only could3’UTR bind to corresponding micro RNAs to inhibit the expression of target genes, but also it terms as an independent RNA molecule to regulate the expression of target genes and related biological activities. What’s more, its abnormal expression may have either cancer promoting or tumor suppressing function. CAPZA1is a member of the F-actin capping protein alpha subunit and has been reported abnormal expression in many tumors. While there haven’t related functional research about the overexpression of CAPZA13’UTR. According to the results of GWAS, we found CAPZA13’UTR overexpression in ESCC samples. Overexpression plasmid was constructed and transfected into ESCC cell line. We selected MTS, clone formation, flow cytometry technology, transwell assay and found that CAPZA13’UTR overexpression could promote cell proliferation and vitality, inhibit cell apoptosis, promote cell invasion, so it hinted that3’UTR might function as an independent RNA molecule to regulate target genes expression or related biological activities, whose overexpression could have tumor promoting function as well. |
