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Preliminary Study On Function Of Long Non-coding RNA In Glioma

Posted on:2015-02-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y SunFull Text:PDF
GTID:1264330428483011Subject:Surgery
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Malignant glioma is a common and severe primary brain tumor with a high recurrencerate and an extremely high mortality rate within2years of diagnosis, even when surgical,radiological, and chemotherapeutic interventions are applied. There are a lot of reasons forfutile therapy on gliomas including: rapid the proliferation, soakage and metastasis of tumorcells, short course, difficult diagnosis of the disease in the early stage, complex lesion location,etc How to find the markers for the and molecular glioma diagnosis and neural targeteffectively for blocking the proliferation and metastasis of tumor cells, improving the therapyefficiency remain to be elucidate.LncRNA is most commonly defned as a non-protein-coding RNA molecule longer than200nucleotides. Evidence suggests that many lncRNAs involved in disease-associatedprocesses such as cancer initiation and progression. lncRNAs are becoming recognized as ahallmark feature of many types of diseases. Importantly, cancer-associated lncRNAs mayserve as diagnostic or predictive biomarkers of cancer and also provide a new therapeuticstrategy of selectively silencing cancer-associated lncRNAs. However, there are stillsignificant gaps in our current understanding of lncRNAfunction in glioma.To study of human long noncoding RNAs on glioma cell proliferation and explore itsmolecular mechanisms. Three cancer-associated lncRNAs including urothelial cancerassociated1(UCA1), metastasis-associated lung adenocarcinoma transcript1(MALAT1),colorectal neoplasia differentially expressed (CRNDE), were validate screened in40groupsof glioma and its adjacent tissue. Their relationship with the pathological type were alsosummarized. Constructed expression vector of UCA1, and exogenously expressed lncRNAUCA1in glioma cell U251. Using colony formation assay, CCK-8cell viability analysis,flow cytometry cell cycle, we tend to explore the influence of lncRNA UCA1on the gliomacell biological function and the possible mechanism.Using qRT-PCR to validate screened three lncRNAs in40groups of glioma and itsadjacent tissues, we found that the expression of MALAT1increase in75%HCC tissues, the percentage of lncRNA CRNDE and UCA1is65%and60%.Expression of three lncRNAswere significantly different in low-grade gliomas (WHO I-II level) and high-grade gliomas(WHO III-IV grade). The eukaryotic expression plasmid of lncRNA UCA1was successfullyconstructed. The Clone forming ability of glioma cell U251was increased by exogenouslyexpressed lncRNA UCA1; CCK-8detection showed that, lncRNA UCA1may accelerate theproliferation of U251; cell cycle analysis showed that, glioma cell with sexogenousexpression of UCA1, in G0/G1phase cells decreased, S phase increased relatively, but G2/Mhad no obvious change, it suggests that UCA1may promote tumor proliferation by affectingthe cell cycle. Our study demonstrates that the expression level was significantly increased3lncRNA CRNDE, MALTA1, UCA1in glioma tissues, and is associated with themalignantdegree of tumor, might be involved in the biological process of glioma cells; lncRNA UCA1can promote the proliferation of glioma cells by affecting the cell cycle.The research mayprovide a new idea on molecular diagnostic markers and potential therapeutic targets forglioma.
Keywords/Search Tags:Glioma, Long non-coding RNA, Cell proliferation, Glioma treatment, ColorectalNeoplasia Differentially Expressed (CRNDE), Urothelial cancer Associated1(UCA1), metastasis-associated lung adenocarcinoma transcript1(MALAT1)
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