Gene expression regulation by miR-145 in pancreatic cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Huang Tai-Chung
PROVIDER: S-ECPF-GEOD-45245 | biostudies-other |
REPOSITORIES: biostudies-other
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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.
| S-ECPF-GEOD-45246 | 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.
2013-03-19 | GSE45245 | 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.
2013-03-19 | E-GEOD-45245 | 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. 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: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.
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Project description:The two unrelated miRNAs miR-143 and miR-145, coexpressed from the miR-143/145 cluster, have been proposed to act as tumor suppressors in human cancer, and therapeutic benefits of delivering miR-143 and miR-145 to tumors have been reported. In contrast, we found that tumor-specific deletion of miR-143/145 in an autochthonous mouse model of lung adenocarcinoma did not affect tumor development. This was consistent with the lack of endogenous miR-143/145 expression in normal and transformed lung epithelium. Surprisingly, miR-143/145 in the tumor microenvironment dramatically promoted tumor growth by stimulating the proliferation of endothelial cells. Loss of miR-143/145 in vivo led to derepression of the miR-145 target CAMK1D, an inhibitory kinase, which when overexpressed prevents mitotic entry of endothelial cells. As a consequence, tumors in miR-143/145-deficient animals exhibited diminished neoangiogenesis, increased apoptosis, and their expansion was limited by the tumor's ability to co-opt the alveolar vasculature. These findings demonstrate that stromal miR-143/145 promotes tumorigenesis and caution against the use of these miRNAs as agents in cancer therapeutics.This study shows that miR-143/145 expressed from the tumor microenvironment stimulates neoangiogenesis and supports tumor expansion in the lung, demonstrating a surprising role for the putative tumor suppressor miRNA cluster in promoting tumorigenesis. We propose inhibition of miR-143/145 as a therapeutic avenue to modulate tumor neoangiogenesis.
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Project description:Recent evidence has demonstrated that circular RNAs (circRNAs) played crucial roles in fine-tuning the levels of gene expression by sequestering the corresponding microRNA (miRNAs). Their interaction with disease-associated miRNAs indicates that circRNAs are important for the development of disease, and miR-145 has been previously shown to have antitumor effect in prostate cancer. In the current study, we successfully established the miR-145-overexpressed prostate cancer LNCaP cells (LNCaP-miR-145) using lentiviral vectors. LNCaP cells expressing the empty vector (LNCaP-NC) were used as the negative control. The circRNA expression in LNCaP-miR-145 cells was detected by microarray analysis, and the miRNA targets of circRNAs were predicted using the bioinformatics software TargetScan and miRanda. Quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of circRNAs in the prostate cancer tissue, nonmalignant tissue, LNCaP-miR-145 cells, and LNCaP-NC cells. The interaction of miRNA and circRNA was further confirmed by the dual-luciferase reporter assay. A total of 267 and 149 circRNAs were significantly up- and downregulated in LNCaP-miR-145 cells, respectively. hsa_circRNA_101981, hsa_circRNA_101996 and hsa_circRNA_09142 were the 3 circRNAs that interacted with hsa-miR-145-5p; hsa_circRNA_008068 and hsa_circRNA_406557 were the 2 circRNAs that interacted with hsa-miR-145-3p. Most of the circRNAs corresponded to the protein-coding exons. The expression levels of hsa_circRNA_101981, hsa_circRNA_00806, and hsa_circRNA_406557 were upregulated in the LNCaP-miR-145 cells, but downregulated in the prostate cancer tissue. In contrast, the expression levels of hsa_circRNA_101996 and hsa_circRNA_091420 were downregulated in the LNCaP-miR-145 cells, but upregulated in the prostate cancer tissue. Moreover, miR-145-5P might regulate the expression of hsa_circRNA_101981, hsa_circRNA_101996, and hsa_circRNA_09142, while miR-145-3P might regulate the expression of hsa_circRNA_008068 and hsa_circRNA_406557. Overexpression of miR-145 promoted the expression of hsa_circRNA_101981, hsa_circRNA_008068, and hsa_circRNA_406557 but suppressed the expressions of hsa_circRNA_101996 and hsa_circRNA_091420 in LNCaP cells. The results from the current study should give us a clue to clarify the tumor suppressive effect of miR-145.
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