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A Study On The Anti-tumor Biological Behavior Effects In Bladder Carcinoma And Mechanisms Of MicroRNA-374a

Posted on:2019-08-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:X L ChenFull Text:PDF
GTID:1364330572952968Subject:Urology
Abstract/Summary:PDF Full Text Request
Bladder tumor is one of the diseases that seriously endanger the health of our people.At present,our traditional clinical treatment of bladder tumors is surgery combined with radiotherapy and chemotherapy.However,traditional chemotherapy methods have limited the application of chemotherapy drugs in clinical treatment due to their high toxic side effects and poor targeting.Therefore,it is necessary to continue to search for new targeted specific anti-bladder tumor drugs.There is increasing evidence that aberrant expression of mi RNAs in various types of malignancies can function as oncogenes or tumor suppressors.These mi RNAs can disrupt tightly controlled RNA networks in cancer cells.The identification of aberrantly expressed mi RNAs may provide important clues for studying the molecular mechanisms of the initiation,progression and metastasis of bladder cancer.Our study found that mi R-374 a plays a key role in the fight against bladder tumors and reverses cisplatin resistance.The main research results of this thesis are as follows:1.Computer simulation analysis found that low levels of mi R-374 a were associated with poor prognosis in patients with bladder cancer who had distant metastases.2.Based on studies of two bladder cancer cell lines,WNT5 A is a direct downstream target gene of mi R-374 a.The mi R-374 a analog can down-regulate WNT5 A signaling to reduce the metastatic potential of human bladder cancer cells T24 and TCCSUP,delaying progression;while mi R-374 a inhibitors show the opposite effect.3.mi R-374 a analogues increased the phosphorylation level reduced and nuclear translocation of β-catenin.4.The apoptosis of bladder cancer cells induced by cisplatin treatment was enhanced and the expression level of stem cell-associated proteins was down-regulated in cells pretreated with mi R-374 a analog.In summary,this study found that mi R-374 a can down-regulate WNT5 A toinhibit Wnt/β-catenin signaling,reduce invasive biological behavior and stem cell characteristics of bladder cancer and reverse cisplatin resistance.This suggests that mi R-374 a may be a novel therapeutic target for bladder cancer patients with low levels of mi R-374 a transcripts.
Keywords/Search Tags:mMir-374a, bladder cancer, metastasis, drug resistance, WNT5A, Wnt/β-catenin
PDF Full Text Request
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