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The Role And Mechanism Of 14-3-3sigma In Intrahepatic Cholangiocarcinoma

Posted on:2019-01-05Degree:MasterType:Thesis
Country:ChinaCandidate:Z J YangFull Text:PDF
GTID:2334330542993037Subject:Surgery
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Background:Cholangiocarcinoma(CC)is the second most common tumor of primary liver cancers in the world.It is generally classified into three forms including intrahepatic cholangiocarcinoma(ICC),hilar cholangiocarcinoma and extrahepatic cholangiocarcinoma(ECC).ICC is an aggressive malignancy with very poor prognosis and increased incidence worldwide recently.Regardless of the advances in diagnostic and therapeutic procedures for liver cancers,the prognosis of ICC patients remains pessimistic.So a better understanding of the molecular mechanisms in the progression of ICC will improve the prognosis of ICC patients.Objective:14-3-3sigma protein plays an important role in multiple cellular processes.The role of 14-3-3 sigma in the progression of intrahepatic cholangiocarcinoma(ICC)has not been well understood.We performed this research to explore the relationship between 14-3-3sigma level and clinical characteristics and prognosis of ICC patients.Besides,we used ICC cell lines HCCC-9810 and RBE to assess the biological function of 14-3-3sigma.Methods:We examined 14-3-3sigma expression in 28 ICC tissues and matched paratumor tissues by quantitative real-time PCR and immunohistochemistry.Additionally,ICC tissue array from 100 patients and normal liver tissue array from 24 healthy people were also analyzed by immunohistochemistry.14-3-3 sigma was knocked down in ICC cell lines and the functions and mechanisms of 14-3-3sigma were assessed.Results:14-3-3 sigma is highly expressed in ICC tissues and high expression of 14-3-3sigma correlates poor overall survival in ICC patients.Knocking down of 14-3-3sigma in ICC cell lines reduced cells migration,invasion and anoikis resistance.Furthermore,14-3-3sigma-silenced ICC cells showed significantly decreased invasion-related protein MMP2 and MMP9 expression.Conclusions:Our results demonstrate prognostic value of 14-3-3sigma and its role in metastasis,which is associated with ICC cell lines migration,invasion and anoikis resistance.
Keywords/Search Tags:14-3-3sigma, intrahepatic cholangiocarcinoma, metastasis, anoikis resistance
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