MiRNAs regulation by miR-145 in pancreatic cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Huang Tai-Chung
PROVIDER: S-ECPF-GEOD-45246 | biostudies-other |
REPOSITORIES: biostudies-other
Similar Datasets
Project description:miR-145 is a tumor suppressor miRNA in various malignancies including pancreatic cancer. How miR-145 regulates expression of other miRNAs could provide a panoramic view of the development of pancreatic cancer. Therefore, in this project, we aimed to characterize how other miRNAs are affected by miR-145 in hope for understanding proteomic changes that are not explained by miR-145 alone. miRNA microarray was used to compare expression of all miRNAs 48 hr after transfection of miR-145 mimics or control scramble RNA in a pancreatic cancer cell line, Mia-PaCa2.
2013-03-19 | E-GEOD-45246 | biostudies-arrayexpress
Project description:miR-145 is a tumor suppressor miRNA in various malignancies including pancreatic cancer. How miR-145 regulates expression of other miRNAs could provide a panoramic view of the development of pancreatic cancer. Therefore, in this project, we aimed to characterize how other miRNAs are affected by miR-145 in hope for understanding proteomic changes that are not explained by miR-145 alone.
2013-03-19 | GSE45246 | GEO
Project description:miR-145 is a tumor suppressor miRNA in various malignancies including pancreatic cancer. Identification of miR-145 targets can lead to more understanding of the development of pancreatic cancer. Therefore, in this project, we aimed to characterize the changes of transcriptomes caused by miR-145 to identify more miR-145 target transcripts. cDNA microarray was used to compare transcriptomes 48 hr after transfection of miR-145 mimics or control scramble RNA in a pancreatic cancer cell line, Mia-PaCa2.
| S-ECPF-GEOD-45245 | biostudies-other
Project description:miR-145 is a tumor suppressor miRNA in various malignancies including pancreatic cancer. Identification of miR-145 targets can lead to more understanding of the development of pancreatic cancer. Therefore, in this project, we aimed to characterize the changes of transcriptomes caused by miR-145 to identify more miR-145 target transcripts. cDNA microarray was used to compare transcriptomes 48 hr after transfection of miR-145 mimics or control scramble RNA in a pancreatic cancer cell line, Mia-PaCa2.
2013-03-19 | E-GEOD-45245 | biostudies-arrayexpress
Project description:miR-145 is a tumor suppressor miRNA in various malignancies including pancreatic cancer. Identification of miR-145 targets can lead to more understanding of the development of pancreatic cancer. Therefore, in this project, we aimed to characterize the changes of transcriptomes caused by miR-145 to identify more miR-145 target transcripts.
2013-03-19 | GSE45245 | GEO
Project description:In microRNA (miRNA) biogenesis, the guide-strand of miRNA integrates into the RNA induced silencing complex (RISC), whereas the passenger-strand is inactivated through degradation. Analysis of our miRNA expression signature of bladder cancer (BC) by deep-sequencing revealed that microRNA (miR)-145-5p (guide-strand) and miR-145-3p (passenger-strand) were significantly downregulated in BC tissues. It is well known that miR-145-5p functions as a tumor suppressor in several types of cancer. However, the impact of miR-145-3p on cancer cells is still ambiguous. The aim of the present study was to investigate the functional significance of miR-145-3p and BC oncogenic pathways and targets regulated by miR-145-5p/miR-145-3p. Ectopic expression of either miR-145-5p or miR-145-3p in BC cells significantly suppressed cancer cell growth, migration and invasion and it also induced apoptosis. The gene encoding ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was a direct target of these miRNAs. Silencing of UHRF1 induced apoptosis and inhibited cancer cell proliferation, migration, and invasion in BC cells. In addition, overexpressed UHRF1 was confirmed in BC clinical specimens, and the high UHRF1 expression group showed a significantly poorer cause specific survival rate in comparison with the low expression group. Taken together, our present data demonstrated that both strands of miR-145 (miR-145-5p: guide-strand and miR-145-3p: passenger-strand) play pivotal roles in BC cells by regulating UHRF1. The identification of the molecular target of a tumor suppressive miRNAs provides novel insights into the potential mechanisms of BC oncogenesis and suggests novel therapeutic strategies.
| S-EPMC5053739 | biostudies-literature
Project description:Glaucoma is a major cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP), which causes optic nerve damage and retinal ganglion cell death, is the primary risk factor for blindness in glaucoma patients. IOP is controlled by the balance between aqueous humor secretion from the ciliary body (CB) and its drainage through the trabecular meshwork (TM). How microRNAs (miRs) regulate IOP and glaucoma in vivo is largely unknown. Here we show that miR-143 and miR-145 expression is enriched in the smooth muscle and trabecular meshwork in the eye. Targeted deletion of miR-143/145 in mice results in significantly reduced IOP, consistent with an ~2-fold increase in outflow facilities. However, aqueous humor production in the same mice appears to be normal based on a microbeads-induced glaucoma model. Mechanistically, we found that miR-143/145 regulates actin dynamics and the contractility of TM cells, consistent with its regulation of actin-related protein complex (ARPC) subunit 2, 3, and 5, as well as myosin light chain kinase (MLCK) in these cells. Our data establish miR-143/145 as important regulators of IOP, which may have important therapeutic implications in glaucoma.
| S-EPMC5430458 | biostudies-literature
Project description:MicroRNAs are master gene regulators that can also be under the control of transcriptional regulation. We have previously shown that miR-145 is a tumor suppressor capable of silencing c-Myc and the tumor suppressor p53 induces miR-145 by directly binding to the miR-145 promoter, demonstrating the role of miR-145 in p53-mediated c-Myc repression. However, little is known as to why miR-145 is often downregulated in tumors. In this study, we identify CCAAT/enhancer binding protein beta (C/EBP-β) as a negative regulator for miR-145 expression by direct interaction with the putative C/EBP-β binding site in the miR-145 promoter. In the wild-type p53 background, C/EBP-β counteracts the ability of p53 to induce miR-145. Moreover, C/EBP-β is able to suppress miR-145 in the mutant p53 background, suggesting the p53 independent regulation of miR-145. Of interest, both the large isoform (LAP-2) and the small isoform (LIP) of C/EBP-β can exert suppressive function for miR-145. Finally, we further show that, like serum starvation and PI3K inhibitor LY29, the antioxidant resveratrol suppresses pAkt and phosphorylation of C/EBP-β and at the same time, it induces miR-145. Together, these results suggest a miR-145 regulatory system involving the Akt and C/EBP-β, which may contribute to the downregulation of miR-145 in cancer cells.
| S-EPMC3413133 | biostudies-literature
Project description:BackgroundThymoma and thymic carcinoma are the most frequent subtypes of thymic epithelial tumors (TETs). A relevant advance in TET management could derive from a deeper molecular characterization of these neoplasms. We previously identified a set of microRNA (miRNAs) differentially expressed in TETs and normal thymic tissues and among the most significantly deregulated we described the down-regulation of miR-145-5p in TET. Here we describe the mRNAs diversely regulated in TETs and analyze the correlation between these and the miRNAs previously identified, focusing in particular on miR-145-5p. Then, we examine the functional role of miR-145-5p in TETs and its epigenetic transcriptional regulation.MethodsmRNAs expression profiling of a cohort of fresh frozen TETs and normal tissues was performed by microarray analysis. MiR-145-5p role in TETs was evaluated in vitro, modulating its expression in a Thymic Carcinoma (TC1889) cell line. Epigenetic transcriptional regulation of miR-145-5p was examined by treating the TC1889 cell line with the HDAC inhibitor Valproic Acid (VPA).ResultsStarting from the identification of a 69-gene signature of miR-145-5p putative target mRNAs, whose expression was inversely correlated to that of miR-145-5p, we followed the expression of some of them in vitro upon overexpression of miR-145-5p; we observed that this resulted in the down-regulation of the target genes, impacting on TETs cancerous phenotype. We also found that VPA treatment of TC1889 cells led to miR-145-5p up-regulation and concomitant down-regulation of miR-145-5p target genes and exhibited antitumor effects, as indicated by the induction of cell cycle arrest and by the reduction of cell viability, colony forming ability and migration capability. The importance of miR-145-5p up-regulation mediated by VPA is evidenced by the fact that hampering miR-145-5p activity by a LNA inhibitor reduced the impact of VPA treatment on cell viability and colony forming ability of TET cells. Finally, we observed that VPA was also able to enhance the response of TET cells to cisplatin and erlotinib.ConclusionsAltogether our results suggest that the epigenetic regulation of miR-145-5p expression, as well as the modulation of its functional targets, could be relevant players in tumor progression and treatment response in TETs.
| S-EPMC5424390 | biostudies-literature
Project description:BACKGROUND:MiR-145 has been identified as a tumor suppressive microRNA in multiple cancers. In this current investigation, we searched for new direct targets of miR-145 and evaluated their effect on breast cancer development. METHODS:Targetscan was used to predict the target genes of miR-145. The targeting of miR-145 on oncogenic HBXIP was verified by luciferase reporter gene analysis. The effect of miR-145 on the level of messenger RNA and protein of HBXIP was evaluated by quantitative real-time PCR and immunoblotting. Correlations between miR-145 and HBXIP, as well as miR-145 expression, were analyzed in 30 paired breast cancer and noncancerous tissues by quantitative real-time PCR. Methyl thiazol tetrazolium and colony formation assays were applied to determine the cell proliferation ability. RESULTS:HBXIP was identified as a novel target gene of miR-145 in breast cancer. MiR-145 was found to dose-dependently decrease messenger RNA and protein expression of HBXIP in breast cancer MCF-7 cells. Notably, miR-145 expression was negatively related to HBXIP expression and was obviously reduced in breast cancer samples. Finally, miR-145 suppressed cell proliferation while its inhibitor, anti-miR-145, accelerated cell proliferation. Interestingly, silencing of HBXIP reversed the acceleration of cell proliferation induced by anti-miR-145 in breast cancer. CONCLUSION:Oncogenic HBXIP is a new direct target of tumor suppressive miR-145. Our findings reveal that miR-145-targeting HBXIP could be a potential therapeutic target in breast cancer.
| S-EPMC6312848 | biostudies-other