Study On The Role And Mechanism Of Malate Dehydrogenase(MDH1) In Cervical Cancer

Aims:By studying the expression of malate dehydrogenase(MDH1)in cervical cancer and its effect on the biological behavior of tumor cells,the role and mechanism of MDH1 in cervical cancer would be discussed.Methods and materials:A total 154 histological specimens of cervical cancer patients were collected from Shanghai Xinchao Biological Co.,Ltd.and the Department of Radiotherapy,Second Hospital of Jilin University from Jan 2010 to Oct2011,the time point of clinical follow-up is Oct 2017.The age of the patients ranged from 29 to 70 years old,of which 68 were older than 45 years old and 51 were younger than 45 years old.According to FIGO staging 2009 standard of cervical cancer,the 119 specimens include 67 in stage I,29 in stage II and 1 in stage III,22 in stage IV;25 in grade 0-I and94 in stage II-III of pathological grade.There were 97 cases of lymph node metastasis and 22 cases of lymph node metastasis.Among them,39 cases of recurrence and 80 cases of non-recurrence.In addition,35 cases of non-neoplastic tissue adjacent to cancer were selected as control group.In these specimens,107 specimens were detected with HPV,and 15 specimens were negative,92 specimens were positive.Immunohistochemical method was used to detect the expression of MDH1 protein in human tissue specimens.The relationship between the expression of MDH1 and clinicopathological characteristics of cervical cancer was analyzed.The correlation between the expression of MDH1 protein and survival rate of cervical cancer was analyzed by survival time analysis.In vitro experiments,HeLa cells were selected as the research object,and the gene of MDH1 was knocked down by small RNA interference technology;the effect of MDH1 on the cloning ability of cervical cancer cells was studied by cloning analysis;the effect of MDH1 on apoptosis of cervical cancer cells was studied by flow cytometry;and the effect of MDH1 on migration and invasion of cervical cancer cells was studied by Wound Healing and transwell experiments.The effect of MDH1 gene knockdown on EMT key marker protein of cervical cancer cells was examed by western blotting,and the role of MDH1 in the development of cervical cancer was studied.Finally,SPSS 17.0 software was used to analyze the data.Results:MDH1 is highly expressed in cervical cancer.The expression of MDH1 in cervical cancer and adjacent non-neoplastic tissues was studied by immunohistochemistry.It was found that the strong positive rate of MDH1 was 5.7%(2/35)in adjacent non-neoplastic tissues and 68.1%(81/119)in cervical cancer tissues,which was significantly different from that inadjacent normal tissues(p < 0.01).There was no significant difference in age,pathological grade,lymph node metastasis and recurrence between patients with high expression of MDH1 and cervical cancer patients,but it was closely related to TNM stage.There was significant difference in expression of MDH1 between patients with stage 4 cervical cancer(p=0.007).The expression of MDH1 was not related to HPV infection.MDH1 expression is associated with survival of cervical cancer.The survival rate of patients with high expression of MDH1 was significantly lower.MDH1 promotes the cloning of cervical cancer cells and inhibits the apoptosis of cervical cancer cells.It can promote the migration and invasion of cervical cancer cells.The mechanism may be related to the regulation of EMT transformation by MDH1 through Snail.Conclusion:The expression of MDH1 protein is significantly higher in cervical cancer than in adjacent tissues,which is closely related to the stage of cervical cancer and predicts a lower survival rate.In vitro,MDH1 may promote the proliferation,migration and invasion of cervical cancer cells by regulating EMT transformation by Snail.MDH1 is expected to become a marker for diagnosis and prognosis evaluation of cervical cancer and would be a new therapy target.