The Relationship Between LncRNA MAPT-AS1, MiR-145-3p And Breast Cancer Resistance And Prognosis

Part ?:Overexpression of MAPT-AS1 is associated with better patient survival in breast cancerObjective:Breast cancer is the most frequent malignant disease in women worldwide.It is a heterogeneous and complex genetic disease with different molecular characteristics.In recent years,more and more long noncoding RNA(lncRNAs)have been identified recently.There was strong evidence that lncRNAs were related with the occurrence and development of malignant tumors.MAPT-AS1,a long non-coding RNA(lncRNA)existing at the anti-sense strand of MAPT(microtubule associated protein tau)promoter region,was believed to regulate MAPT which was associated with disease state in Parkinson's disease.But the role of MAPT-AS1 in breast cancer has never been reported.To detect the MAPT-AS1 expression in patients with breast cancer and to explore its association with prognosis.In order to make clear whether MAPT-AS1 can be prognostic factor for prognosis of breast cancer and provide the basis for further research.Methods:60 breast cancer patients were studied in this part.The expression level of MAPT-AS1 in tumor tissues was detected by PCR,and its correlation with survival of breast cancer was analyzed.Results:MAPT-AS1 is overexpressed in breast cancer but not in triple negative breast cancer(TNBC),and high expression of MAPT-AS1 was correlated with better patient survival.In addition,the level of MAPT-AS1 was correlated with expression of MAPT and MAPT was associated with survival time in breast cancer.Conclusions:MAPT-AS1 may play a role and be a potential survival predictive biomarker in breast cancer.Part ?:miR-142-3p reversed Endocrine Resistance in Breast Cancer via Inhibition of HMGB1Objective:Breast cancer has become the highest incidence malignant tumors in women in China.The treatment of breast cancer is no longer just with surgical treatment,but also the new mode of systemic treatment.The chemotherapy is the treatment standard in the edition of Chinese Association for breast cancer treatment guidelines and norms.But patients have significant difference in the response to the treatment because of heterogeneity of disease and individual differences.Screening the markers for prediction of chemotherapy sensitivity will be valuable to evaluate chemotherapy and explore the mechanism of drug resistance in breast cancer chemotherapy.HMGB1(high mobility group box 1)is a protein encoded by the human HMGB1 gene and has the effect of promoting tumor survival,growth,and metastasis.MicroRNA(miRNA)is endogenous short-chain RNA.Currently studies have found a variety of microRNA involved in development and treatment resistance of breast cancer.miRNA has been found to be involved in cancer drug resistance through a variety of ways,such as promoting cancer cell invasion,causing damaging DNA repairing cell damage reaction and decreasing the drug concentration.We analyzed drug resistant cell lines and sensitive cell lines by microRNA microarray,and we found that 5 microRNAs were expressed abnormally.RT-PCR was used to detect the difference of them,and the result showed that only miR-142-3p was elevated in drug resistant cell lines.Therefore,we speculate that it plays a role in resistance to therapy in breast cancer.There were few research on serum miRNA and its correlation with breast cancer drug resistance.We next detected serum miRNA expression in breast cancer patients and predicted it as a marker for progonosis.Methods:We analyzed drug resistant cell lines and sensitive cell lines by microRNA microarray,RT-PCR was used to detect the difference of them.Analyze the clinic information of patients with chemotherapy of Jiangsu Tumor Hospital from 2010 to 2015 and find related factors that affect the therapeutic effects.Compare the differences of serum miRNA expression between the chemotherapy resistance group and the sensitive group with miRNA gene chip.Verify the differences of serum miR-142-3p between the two groups by RT-PCR.The expression level of HMGB1 were verified by PCR and Western blot.Results:miR-142-3p was decreased significantly in drug resistant cell lines.The incidence of drug resistance in 106 patients with chemotherapy was 28.3%.In baseline data,there is no significant difference in the age,tumor size,lymph node metastasis and clinical stage of patients.Statistical results show that ER positive and ER negative group,PR positive group and PR negative group chemotherapy curative effect is different and have significant difference.Through comparing the serum miRNA of the chemotherapy resistance group and the sensitive group,we found 12 upregulated miRNAs and 20 downregulated miRNAs in statistical significance.Serum miR-142-3p expression in chemotherapy resistance group is lower than sensitive group.The breast cancer cells sensitived to TAM through regulating miR-142-3p expression to increase the level of HMGB1.Conclusion:miR-142-3p was decreased in drug resistant cell lines.Serum miR-142-3p was lowly expressed in chemotherapy resistance group,indicating serum miR-142-3p could be used as a predicted biomarker of drug resistance in breast cancer patients.It also has clinical application since the detection of serum miR-142-3p is convenient and quick.The breast cancer cells sensitived to TAM through regulating miR-142-3p expression to increase the level of HMGB1.