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Role Of Long Non-coding RNA In Glioma

Posted on:2015-04-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y DingFull Text:PDF
GTID:2284330485995081Subject:Neurosurgery
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Aberrant expression of long non-coding RNAs (lncRNAs) has been implicated in various diseases, including cancer. However, little is known about lncRNAs in human brain glioma. Here, we describe lncRNA profiles from three glioma specimens using lncRNA expression profiling microarrays. We found 4858 lncRNAs to be differentially expressed between tumor tissue and peritumoral tissue. Of these,2845 lncRNAs were up-regulated (fold change> 3.0) and 2013 were down-regulated (fold change< 1/3). A total of 4084 messenger RNAs were also differentially expressed, including 2280 up-regulated transcripts (fold change> 3.0) and 1804 that were down-regulated (fold change< 1/3). Based on multiple criteria, including significance of differential expression, raw intensitiesof lncRNA expression in normal tissue, and quantitative real-time RT-PCR (qPCR) analysis of glioma and peritumoral tissue from 40 patients,6 lncRNAs (akl25809, ak098473, uc002ehu.1, bc043564, NR027322, and uc003qmb.2) were chosen for further study. Consistent with the microarray data, qPCR confirmed differential expression of these 6 lncRNAs between tumor and peritumoral tissue. We next established co-expression networks of differentially expressed lncRNAs and mRNAs. Many mRNAs, such as LOC729991, NUDCD1, SHC3, PDGFA, and MDM2, and lncRNAs, such as ENST00000425922, ENST00000455568, uc002ukz.1, ENST00000502715, and NR027873 have been shown to play important roles in glioma development. Consistent with this, pathway analysis revealed that "GLIOMA" (KEGG PathwaylD:hsa05214)was significantly enriched in tumor tissue. Taken together, our data suggest that altered expression of lncRNAs may be a critical determinant of tumorigenesis in glioma patients. We aimed to investigate the SPRY4-IT1 expression level in glioma, and the role of SPRY4-IT1 in glioma U87 cell biological functions. Quantitative real-time polymerase chain reactions for SPRY4-IT1 expression were performed in 40 pairs of glioma tissues and adjacent tissues. Lentiviral-mediated SPRY4-IT1 knockdownin U87 was further to investigate its role in glioma cell biological functions. Cell growth, apoptosis and migration were tested in vitro by CCK-8 assays, flow cytometry and transwell assays, respectively. SPRY4-IT1 expression was significantly overexpressed in cancer tissues (P<0.05).Knockdown of SPRY4-IT1 expression reduced cell migration (P<0.05), but have no significant changes in cell growth (P>0.05) and cell apoptosis (P>0.05). SPRY4-IT1 was overexpressed in glioma tissues and promoted the migration of U87 cells. The expression of long non-coding RNA SPRY4-IT1 may play an important role in the process of glioma development and may be developed as a useful biomarker for the diagnosis and prognosis of glioma.
Keywords/Search Tags:glioma, lncRNA, microarry, co-expression network, SPRY4-IT1
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