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Expression And Significance Of QKI-5 In Triple Negative Breast Cancer

Posted on:2017-09-27Degree:MasterType:Thesis
Country:ChinaCandidate:C LiFull Text:PDF
GTID:2404330590969466Subject:Clinical Laboratory Science
Abstract/Summary:PDF Full Text Request
Alternative splicing is crucial for the regulation of gene expression and a source for generating proteomic and functional diversity,also it has an important role in cell growth and differentiation.Aberrant splicing causes a large range of human diseases including cancers.Many evidences show that splicing regulators are often dysregulated in cancers.QKI is a crucial RNA-binding protein which belongs to STAR(Signal Transduction and RNA Activation)protein family,it plays an important role in alternative splicing,also it can regulate mRNA stability,QKI-5 protein is an important QKI isomer,currently,QKI-5 has been reported to be associated with initiation and development of a variety of tumors.Women have a high incidence for breast cancer,triple negative breast cancer is a type of breast cancer that its ER,PR and HER2 are negative,it also has a high degree of malignancy,metastasis occurs frequently,yet,there are no research about QKI-5 and triple negative breast cancer.Firstly,to explore the relationship between the expression of QKI-5 in tumor tissues compared with para-carcinoma tissues and clinical pathological parameters,we detected the expression of QKI-5 in 30 pairs of tumor tissues and relative para-carcinoma tissues of triple negative breast cancer by using IHC.Results showed that: 1.The expression of QKI-5 were lower when compared to para-carcinomatissues.The expression of QKI-5 was not related to the patients' age,pathological grade(P>0.05),but,it was highly related to the lymph node metastasis and tumor size(P<0.05),the results showed that the expression of QKI-5 may be associated with lymph node metastasis in triple negative breast cancer.Secondly,using lentiviral vectors,we established two stable triple negative breast cancer cell lines with altered QKI-5 expression,including a QKI-5 overexpressing MDA-MB-231 cell line and a 4T1 cell line with knocked-down QKI-5 expression.The effects of the lentiviral-mediated QKI-5 on the 4T1 cells and MDA-MB-231 cells were assessed by migration assay.Results showed that the migration of QKI-5 overexpressing MDA-MB-231 cell line was significantly inhibited in vitro(P<0.05),the migration of QKI-5 knocked-down 4T1 cell line was effectively promoted invitro(P<0.001),also we investigated the mechanism that QKI-5 influences the migration of triple negative breast cancer cell by western blot.Results showed that QKI-5 inhibits the EMT process of triple negative breast cancer cell line.This part of reserch showed that QKI-5 may influence migration of triple negative breast cancer cell by EMT.In conclusion,our research found the expression of QKI-5 in tumor tissues were lower compared with adjacent tissues in tissue samples for the first time,and it was found that the expression of QKI-5 was highly related to the lymph node metastasis in tumor tissue.We also found QKI-5 may inhibit the migration of triple negative breast cancer cell lines through EMT,it provided a new idea for the reserch about the relationship between QKI-5 and triple negative breast cancer.
Keywords/Search Tags:RNA binding protein QKI-5, breast cancer, low expression, inhibition
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