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Effects And Mechanism Of MiR-148a In Biological Behavior Of Breast Cancer

Posted on:2018-10-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q Y LiFull Text:PDF
GTID:1314330515983371Subject:Medical imaging and nuclear medicine
Abstract/Summary:PDF Full Text Request
MicroRNAs(miRNAs)contribute to tumorigenesis through the modulation of tumor-related genes.MiR-148a has been characterized as a tumor-suppressing miRNA and its downregulation has been reported in tumors of a variety of cancers.However,the functional role of MiR-148a in breast cancer is not yet fully understood.Using both in vitro and in vivo models,we confirmed that miR-148a acts to inhibit proliferation of breast cancer cells.Through the use of bioinformatic approaches in miRNA target prediction,we determined that B cell lymphoma 2(BCL-2)is a likely target of miR-148a.The overexpression and tumorigenic effects of BCL-2 have already been confirmed in cancerous tumors of the breast.A dual-luciferase assay was performed to confirm that miR-148a targets the 3’-untranslated region(UTR)of BCL-2.In this study,we first characterized the downregulation of miR-148a in breast cancer tissues.We then found that restoring expression of miR-148a suppressed the expression of BCL-2 at the level of both mRNA and protein.Upregulation of miR-148a caused a subsequent reduction of proliferation and an increase in apoptosis.In conclusion,we have confirmed the role of miR-148a as a pivotal regulator in breast cancer through its targeting of BCL-2.This evidence strongly suggests that miR-148a could prove to be a novel therapeutic target in breast cancer.
Keywords/Search Tags:Breast cancer, MiRNAs, BCL-2, Apoptosis, Proliferation
PDF Full Text Request
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