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Function And Molecular Mechanism Of Long Non-coding RNA MYU In Prostate Cancer Cells

Posted on:2019-07-05Degree:MasterType:Thesis
Country:ChinaCandidate:J H WangFull Text:PDF
GTID:2334330542999355Subject:Cell biology
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Prostate cancer is a urinary malignancy that seriously affects men's health.In recent years,a large number of scientific researches on long non-coding RNA(IncRNA)have shown that IncRNAs are closely related to human malignancies.They usually play a very important role in the development,progression and metastasis of tumors.Many IncRNAs have been found dysregulating in prostate cancer.Here,we analyzed the clinical data of cancer patients from The Cancer Genome Atlas(TCGA)database and found that IncRNA MYU also known as VPS9D1-AS1(VPS9D1 antisense RNA 1),is significantly higher in many human cancer tissues(including prostate cancer tissues)than corresponding normal adjacent tissues,indicating that MYU may be a broad-spectrum highly expressed IncRNA.Our main concern is the role of IncRNA MYU in prostate cancer.In prostate cancer,the MYU promoter region is significantly hypomethylated,which may be one of the underlying causes of its high expression.First,we successfully cloned IncRNA MYU and proved that it does not have protein coding capacity.The results of subcellular faction showed that AYU is distributed both in the nucleus and in the cytoplasm.We also demonstrated that there is no expression regulation relationship between IncRNA MYU and the coding gene VPS9D1.Then.we further found that knockdown of MYU results in the reduction of prostate cancer cells proliferation and migration in vitro.In contrast,overexpression of MYU could promote the aggressive behaviors of prostate cancer cells.Furthermore,IncRNA MYU can be transported into extracellular milieu by means of exosomes,and then promotes adjacent cell proliferation and migration.Mechanismally,the results of dual luciferase reporter assays demonstrated that miR-184 significantly inhibited the luciferase activity of MYU and the proto-oncogene c-Myc 3' untranslated region(UTR).MYU may upregulate c-Myc expression through competitive binding to miR-184.Taken together,our findings indicate that IncRNA MYU may exert oncogenic function in prostate cancer cells,and mediate upregulation of c-Myc by functioning as a competing endogenous RNA(ceRNA)to participate in prostate cancer tumorigenesis and progression.MYU may serve as a new prognostic biomarker and potential novel therapeutic target for prostate cancer.
Keywords/Search Tags:prostate cancer, long non-coding RNA, MYU, miR-184, c-Myc
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