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Study On The Function And The Molecular Mechanism Of LncRNA PTENP1in Renal Clear Cell Carcinoma

Posted on:2015-11-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:W M YaoFull Text:PDF
GTID:1224330428965807Subject:Surgery
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Objective To study the expression, regulation, function and molecular mechanism of long noncoding RNA (lncRNA) PTENP1in human renal clear cell carcinoma (RCCC).Methods Study the expression signatures of lncRNAs in human renal clear cell carcinoma by microarray and qRT-PCR. Expression of PTENP1was examined by qRT-PCR and MSP was performed to analysis the methylation state. The expression correlation of PTENP1and PTEN was examined by qRT-PCR. Luciferase reporter assay was performed to confirm the targeting of miR-21to PTENP1and PTEN. The biological function assays of PTENP1, miR-21and PTEN in cell proliferation, migration and invasion and tumour growth and metastasis were performed in vitro and vivo. The effect of PTNE and miR-21on the function of PTENP1in RCCC was performed.Results Thousands of lncRNAs were detected in RCCC and hundreds of them were differentially expressed in all RCCC samples. PTENP1was down regulated in RCCC and aberrant methylation was detected in PTENP1promoter. PTENP1and PTEN suppresses proliferation, migration and invasion of RCCC. This was a direct correlation between PTENP1and PTEN expressions. Over expression of PTENP1could improve the expression of PTEN. Mir-21was up regulated in RCCC and targeting both PTENP1and PTEN. Mir-21presented tumour promoting function in RCCC. Mir-21could suppress the tumour suppressor function of PTENP1in RCCC in vitro and in vivo.Conclusion LncRNA PTENP1which was down regulated by DNA methylation functions as PTEN competing endogenous RNA (ceRNA) with the dependency of miR-21to suppress RCCC progression.
Keywords/Search Tags:Renal clear cell carcinoma, Long noncoding RNA, PTENP1, Tumoursuppressor, Competing endogenous RNA
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