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Effect Of Uc.338 On Cell Proliferation Of Colorectal Cancer Cells And Related Mechanisms

Posted on:2019-08-12Degree:MasterType:Thesis
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:2404330548951022Subject:Surgery
Abstract/Summary:PDF Full Text Request
[Background] Colorectal cancer(CRC)is one of the most malignant tumors in the world with the highest incidence and mortality,and the incidence of CRC are still on the rise.Tumor stage is vital important for the therapeutic treatment and prognosis of patients diagnosed with CRC.However,most patients diagnosed with CRC have developed into advanced stage,which leads to a significant decrease in the therapeutic effect and the overall survival of these patients.Therefore,to improve the early diagnosis of patients with CRC,understanding the pathogenesis of this disease is very important.[Objective] The study aims to investigate the role of uc.338 in cell proliferation of CRC,and further detect the potential mechanism how uc.338 plays the biological function in CRC.[Materials and methods] The expression levels of uc.338 in human CRC tissues and adjacent normal tissues were detected by quantitative real-time PCR(q RT-PCR).Then the relationship between uc.338 expression and clinicopathological features was further analyzed by Pearson ?2 tests.In cell experiments,the expression level of uc.338 in CRC cell lines and the normal epithelial cell line were firstly detected by q RT-PCR.After uc.338 was knocked down by the si RNA,the CCK-8 assay,plate colony formation assay and Edu assay were used to detect the effect of uc.338 on cell proliferation;Flow cell cycle analysis and flow cell apoptosis analysis were usedto detect the effect of uc.338 on the regulation of cell cycle and cell apoptosis.In vivo,the effect of uc.338 on the cell proliferation in mice was detected by the subcutaneous tumor-bearing experiment.Finally,the relationship between uc.338and PI3K/AKT pathway was detected by western blot.[Results] The results of q RT-PCR showed that the expression of uc.338 was significantly increased in CRC tissues,and the expression of uc.338 was related to the tumor size,the depth of tumor invasion,lymph node metastasis and tumor stage.After uc.338 was knocked down in CRC cells,the results of CCK-8 assay,plate colony formation assay and Edu assay showed that uc.338 could promote cell proliferation;the results of flow cell cycle analysis and flow cell apoptosis analysis showed that uc.338 could promote cell cycle G1/S transition,but no obvious relationship with apoptosis was found.In vivo experiments,the results of subcutaneous tumor experiments revealed that uc.338 could promote tumor growth in nude mice.Finally,Western blot indicated that uc.338 might target p21 downregulation and cyclin D1 upregulation via the PI3K/AKT pathway in CRC cells.[Conclusion] uc.338 was upregulated in CRC tissues and was related to the tumor size,the depth of tumor invasion,lymph node metastasis and tumor stage.uc.338 could promote cell proliferation possibly by cell cycle regulation in CRC cells,and may play these oncogenic functions in CRC possibly by Cyclin D1 upregulation and p21 downregulation through the PI3K/AKT pathway.
Keywords/Search Tags:colorectal cancer, uc.338, PI3K/AKT pathway, Cyclin D1, p21
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