The Expression And Functional Mechanism Of RNA Binding Protein QKI-5,SLC16A3 And Ezrin In Ovarian Serous Cancer

Backgroud:Ovarian cancer is one of the most common malignant tumor which comes from female reproductive system,and its incidence is secondary to cervical cancer and endomentrial cancer.The five years survival of ovarian cancer is ranging from 30% to 50% just because of lacking a sensitive early diagnostic indicator and most of terminal ovarian cancer patients was prone to complication and multi-drug resistance.RNA binding protein is a molecular family that found has significant biological functions in recent years.RBPS can participate in many biological processes by altering the post-transcription of genes which affects the characteristics of cells.More and more researchs show that RBPs have an important relationship with cancer.QKI-5 as an important RNA binding protein can bind with the QKI response elements which located in mRNA and finally affect the location of RNA and stabilty of mRNA.The research proves that completely or patial missing of QKI-5 obstruct central nervous system development,and the lower expression of QKI-5 was found in a lot of malignant tumors such as lung cancer,colorectal cancer,oral cancer,breast cancer and so on.Even though many internal and external expriments comfirmed that the lower expriment of QKI-5 has a significant relationship with the tumor develops,in ovarian cancer,we also need more attention on QKI-5.We all kown that Ezrin and SLC16A3 as the most common menbrane-cell skeleton linking protein and menbrane protein separately has played an important role in the development of tumors.Some researches show that SLC16A3 and Ezrin were high expressed in some malignant tumors such as lung cancer,breast cancer,prostate cancer and osteosarcoma.Ezrin participate in the development of tumors through altering cellular structure stability and adjusting cell signalling pathways,but SLC16A3 fuctions as the transporter which promotes lactic acid metabolism and maintain cellular activity.Even so,there still lack of relative fuction and mechanism researches focused on epithelial ovarian cancer.Methods:Collecting 134 cases of ovarian serous cancer formalin-fixed paraffin-embedded tissues and 23 cases of normal ovarian epithelium,then we use immune chemistry technology to test and analysis the expression and meaning of QKI-5、Ezrin and SLC16A3 with clinical pathology.Collecting 40 cases of ovarian serous cancer fresh tissuses and 27 cases of normal ovarian epithelium,then we use the method of RT-PCR to test the m RNA level of QKI-5、Ezrin and SLC16A3.Constructing the overexpression and knockdown plasmid of QKI-5 and SLC16A3,then we test the relative ability of QKI-5 and SLC16A3 in ovarian cancer cell lines A2780 and SKOV3 through proliferation,apoptotic,transwell-migration,transwell-invasion and cell cycle experiments.We also use chemotherapy drugs sensitivity experiments to test the drug-resistant alteration of SLC16A3 on ovarian cancer cells.Using Subcutaneous tumor formation assay and tail introvenous transfer assay to test the function of QKI-5 on the Tumorigenic and blood transfer ability of ovarian cancer cells.Results:Compared to normal control,Ezrin and QKI-5 have down-regulated significantly in 134 cases of ovarian serous cancer tissues,but of contrast,SLC16A3 was found up-regulated.By analysing the epression of these genes with clinical pathology we can get these results that the lower expressed QKI-5 and Ezrin has a great relationship with ovarian cancer’s clinical stages,clinical grades,Omentum majus metastasis,and survival(p<0.05).However,the Patients with high expression of SLC16A3 has stronger resistance to chemotherapy drugs(p<0.05).We also found that the m RNA level of Ezrin and QKI-5 was down-regulated,however the m RNA level of SLC16A3 was up-regulated and this differences was meaningful statistically.Both in vivo and in vitro expriments confirmed that overexpressing QKI-5 can increase the ratio of G1 phase,and also can reduce the ability of proliferation,migration and invasion of ovarian cancer cell lines.We can suppress the the tumorigenic and blood transfer ability of ovarian cancer cells by overexpressing QKI-5.SLC16a3 can increase the ratio of S phase,and also can enhance the ability of proliferation,migration and invasion of ovarian cancer cell lines,and what’s more,SLC16A3 can promote the survival and apoptosis-resistant ability by reducing the chemosensitivity of SKOV3 and A2780 to platinum.Conclutions:QKI-5,Ezrin and SLC16A3 have abnormal expression in ovarian cancer and this differences has important clinical significance.QKI-5 and SLC16A3 plays the role of tumor suppressor gene and oncogene separately in the process of ovarian cancer development.QKI-5,SLC16A3 and Ezrin were expected to be a target for early diagnosis,prognosis and chemotherapy of ovarian cancer.