Project description:Tremendous studies have found that the abnormality of long noncoding RNA (lncRNA) contributed to cancer initiation, progression, and recurrence via multiple signaling cascades. Nevertheless, the possible underlying mechanisms of lncRNA in temozolomide (TMZ)-resistant glioma were not well understood, hindering the improvement of TMZ-based therapies against glioma. The present study illustrated that the lncRNA KCNQ1OT1 increased in TMZ-resistant gliomas cells compared to the parental cells. Introduction of KCNQ1OT1 boosted glioma cell viability, clonogenicity and rhodamine 123 efflux while hampered apoptosis post-exposure to TMZ. Consistent with bioinformatic prediction, KCNQ1OT1 directly sponged miR-761, which was downregulated in TMZ-resistant glioma cell lines. Overexpression of miR-761 attenuated glioma cell viability and clonogenicity while triggered apoptosis and rhodamine 123 cellular accumulation post-exposure to TMZ, leading to rehabilitated glioma TMZ-sensitivity, which was against the function of KCNQ1OT1. miR-761 bound to 3’-untranslated region of PIM1, a proto-oncogene with constitutive serine/threonine kinase activity, attenuated PIM1-mediated signaling cascades. Furthermore, stable knockdown of KCNQ1OT1 by small hairpin RNA amplified the TMZ-induced tumor regression in TMZ-resistant U251 mouse models. Briefly, the present study evaluated KCNQ1OT1 conferred TMZ resistance by sponging miR-761 and releasing PIM1 expression, resulting in activation of PIM-mediated MDR1/c-Myc/Survivin signaling pathways. The findings mentioned above extended the knowledge of lnRNA KCNQ1OT1 in the regulation of chemoresistance in glioma and provided a promising therapeutic target for TMZ-resistant glioma patients. Long noncoding RNA profiling by array
Project description:To identify TGF-β regulated lncRNAs in glioblastoma, we performed a genome-wide microarray screen in T98G glioma cells. T98G cells were treated with 10 ng/ml TGF-β (24h) and differentially expressed lncRNAs were identified using microarray in comparison with control cells.
Project description:Glioblastomas show heterogeneous histological features. These distinct phenotypic states are thought to be associated with the presence of glioma stem cells (GSCs), which are highly tumorigenic and self-renewing sub-population of tumor cells that have different functional characteristics. We found that TUG1, a long non-coding RNA (lncRNA), plays pivotal roles in maintaining the self-renewal properties of GSC. Some lncRNAs are known to act as a miRNA sponge in the cytoplasm, where lncRNAs bind to miRNAs and quench their activity. To investigate miRNA expression profiling in GSC upon TUG1 inhibition, we have performed microarray experiment using SurePrint G3 Human miRNA 8x60K Microarray (G4872A, Agilent Technologies).
Project description:To explore the potential involvement of lncRNAs in pancreatic ductal adenocarcinoma (PDAC) oncogenesis, we conducted lncRNA profiling in six pairs of human PDAC and adjacent normal tissue by microarray. Our results showed that clusters of lncRNAs were aberrantly expressed in PDAC compared with normal samples, and provided potential targets for future treatment of PDAC and novel insights into PDAC biology.
Project description:To investigate the potential pathogenic mechanism of glioma-related epilepsy (GRE), we have employed analyzing of the dynamic expression profiles of microRNA/ mRNA/ lncRNA in brain tissues of glioma patients. Brain tissues of 16 patients with GRE and nine patients with glioma without epilepsy (GNE) were collected. The total RNA was dephosphorylated, labeled, and hybridized to the Agilent Human miRNA Microarray, Release 19.0, 8x60K. The cDNA was labeled and hybridized to the Agilent LncRNA+mRNA Human Gene Expression Microarray V3.0, 4x180K. The raw data was extracted from hybridized images using Agilent Feature Extraction, and quantile normalization was performed using the Agilent GeneSpring. We found that three differentially expressed miRNAs (miR-10a-5p, miR-10b-5p, miR-629-3p), six differentially expressed lncRNAs (TTN-AS1, LINC00641, SNHG14, LINC00894, SNHG1, OIP5-AS1), and 49 differentially expressed mRNAs may play a vitally critical role in developing GRE.