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The Role And Clinical Significance Of Hsa-miR-24-3p In Human Breast Cancer

Posted on:2020-06-06Degree:MasterType:Thesis
Country:ChinaCandidate:J WuFull Text:PDF
GTID:2404330623957912Subject:Pathology and pathophysiology
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Breast cancer is one of the most common malignant tumors in the world,and it is also one of the most important causes of death for women.In recent years,the incidence of breast cancer in both European and American countries and Asian countries has increased unabated,and there is a trend of younger.High rhythm of life and environmental pollution may be related to the high incidence of breast cancer.For breast cancer,the current main treatment is surgical total mastectomy with lymph node dissection,adjuvant radiotherapy or chemotherapy.Hormone dependent breast cancer can be treated with adjuvant endocrine therapy drugs.Molecular targeted therapy is also a relatively rapid development in recent years.For the current treatment of breast cancer,long-term drug use often leads to drug tolerance,including chemotherapy drugs,endocrine therapy drugs,etc.even if the targeted treatment drug Herceptin,HER2 positive breast cancer patients also have primary drug resistance,long-term use of drugs will also lead to acquired drug resistance,so the development of new treatment drugs,especially for the current refined drugs The concept of quasi therapy and individualized therapy,and the development of new molecular targeted therapy,are urgent problems to be solved.In view of breast cancer,scientists have carried out in-depth research on its molecular mechanism,including tumor promoter gene,tumor suppressor gene,noncoding RNA including miRNA,long noncoding RNA,etc.,which play an important role in it.However,due to its high tumor heterogeneity and complex molecular mechanism,further molecular mechanism exploration on breast cancer is still a large number of researchers Direction of commitment.In this project,based on the archived specimens of the pathology department of the First Affiliated Hospital of Anhui Medical University,we successfully selected 112 paraffin tissue specimens of breast cancer and 21 paraffin tissue specimens of breast benign lesions,and detected the tissue proto expression of miR-24-3p by tissue in situ hybridization.The results showed that the expression level of miR-24-3p in breast benign lesions was significantly higher than that of milk Adenocarcinoma.Furthermore,we analyzed the correlation between the clinical characteristic pathological parameters and the corresponding expression level of miR-24-3p in 112 breast cancer patients.The results showed that the expression level of miR-24-3p was significantly negatively correlated with the number of axillary lymph node metastasis and TNM stage of breast cancer patients,while it was negatively correlated with other characteristic pathological parameters including the age of patients,tumor diameter,tumor tissue,the expression of ER,PR and HER2 were not significantly correlated.The Kaplan Meier curve showed that the expression level of miR-24-3p was positively correlated with the recurrence free survival(RFS)and overall survival(OS)of 112 breast cancer patients,so the high expression of miR-24-3p was favorable the prognosis of the patients recovered.In this paper,the specific mechanism of miR-24-3p was further explored,and the target gene RNF2 of miR-24-3p was found by Target Scan online tool.Luciferase Report experiment proved that miR-24-3p specifically targeted the 3-terminal non coding region of RNF2,inhibited its luciferase activity.The real-time fluorescence quantitative PCR experiment further proved that the overexpression of miR-24-3p inhibited the mRNA level of RNF2 in MCF-7 cells,and the knockdown of miR-24-3p increased the mRNA level of RNF2 in MCF-7 cells.Therefore,miR-24-3p targets RNF2 gene and specifically suppresses its expression.RNF2 has been proved to be an important oncogene of breast cancer in the previous articles of our research group,which can significantly promote the proliferation,metastasis and invasion of breast cancer cells,and has a positive correlation with poor clinicopathological parameters of breast cancer patients.Therefore,miR-24-3p targeted regulation of RNF2 signaling pathway plays an important role in the functional regulation of breast cancer cells and the occurrence,development and malignant progress of patients.In this paper,we further proved that the expression level of miR-24-3p in breast cancer tissue was significantly negatively correlated with the expression level of RNF2 by Pearson correlation analysis.In this study,the important anti-cancer function of miR-24-3p in breast cancer patients was identified,and the specific molecular mechanism was found.miR-24-3p can be used as a potential target treatment drug for breast cancer.
Keywords/Search Tags:miR-24-3p, RNF2, breast cancer, pathology, tumor suppressor
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