ADAR1 controls the miR-381-3p-mediated expression of MRP4 by regulating the production of circHIPK3 in human renal cell
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PROVIDER: PRJNA792611 | ENA |
REPOSITORIES: ENA
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Project description:Multidrug resistance-associated protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is highly expressed in the kidney of mammals and responsible for renal elimination of various drugs. Adenosine deaminase acting on RNA 1 (ADAR1) has been reported to regulate gene expression through catalyzing adenosine-to-inosine (A-to-I) RNA editing. In this study, we found that the down-regulation of ADAR1 increased the expression of MRP4 in human renal cells at post-transcriptional level. The results of luciferase reporter assays and microarray analysis revealed that down-regulation of ADAR1 decreased the levels of miR-381-3p, which led to the up-regulation of MPR4 expression. Circular RNAs (circRNAs) are a kind of closed loop endogenous non-coding RNAs that play a critical role of gene expression by acting as miRNA sponges. ADAR1 repressed the biogenesis of circular RNA circHIPK3 by catalyzing A-to-I RNA editing, which changed the secondary structure of precursor of circHIPK3. In silico analysis suggested that circHIPK3 acted as a sponge of miR-381-3p. Indeed, overexpression of circHIPK3 up-regulated the expression of MRP4 through interfering with miR-381-3p. Our results provide the novel point of view for regulating mechanism of the expression of xenobiotic transporters through mediating the control of circRNA expression by RNA editing enzyme ADAR1.
2022-07-27 | GSE192692 | GEO
Project description:To investigate the mechanism of miR-381-3p in the OIR mice retinal tissues OIR mice.
2023-05-05 | GSE231376 | GEO
Project description:circHIPK3 silencing impairs ß-cell functions leading to a decrease in insulin secretion, proliferation, and survival. Therefore, we wanted to identify the mode of action of circHIPK3 by measuring gene expression changes upon circHIPK3 silencing in MIN6B1 cells.
2018-01-29 | GSE105097 | GEO
Project description:Aortic valve calcific disease (CAVD) is a common heart valve condition typically characterized by severe narrowing of the aortic valve. Our previous research has shown that circHIPK3 is downregulated in calcified aortic valve tissues and plays a role in regulating the progression of CAVD. To further investigate how circHIPK3 exerts its inhibitory effects on aortic valve calcification, we overexpressed circHIPK3 in aortic valve interstitial cells and conducted RNA-seq analysis, revealing that circHIPK3 regulates key factors in the Wnt signaling pathway. These findings contribute to a deeper understanding of the molecular mechanisms underlying CAVD, particularly the potential involvement of circRNAs in this disease.
2024-02-02 | GSE254394 | GEO
Project description:The introduction of new therapies against particular genetic mutations in non-small cell lung cancer is a promising avenue for improving the survival of these patients, but the target population is small. There is a need to uncover new potential actionable genetic lesions and non-conventional cancer pathways, such as RNA editing, are worthy to explore. Herein we show that the adenosine-to-inosine editing enzyme ADAR1 undergoes gene amplification in non-small cancer cell lines and primary tumors in association with higher levels of the corresponding mRNA and protein. From a growth and invasion standpoint, the depletion of ADAR1 expression in amplified cells reduces their tumorigenic potential in cell culture and mice models, whereas its overexpression causes the opposite effects. From a functional perspective, ADAR1 overexpression enhances the editing frequencies of target transcripts such as NEIL1 and miR-381. In the clinical setting, patients with early stage lung cancer, but harboring ADAR1 gene amplification, show poor outcome. Overall, our results indicate a role for ADAR1 as a lung cancer oncogene undergoing gene amplification-associated activation that affect downstream RNA editing patterns and patient prognosis.
2018-04-08 | GSE67660 | GEO
Project description:Multidrug resistance-associated protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is highly expressed in the kidneys of mammals and is responsible for renal elimination of numerous drugs. Adenosine deaminase acting on RNA 1 (ADAR1) has been reported to regulate gene expression by catalyzing adenosine-to-inosine RNA editing reactions; however, potential roles of ADAR1 in the regulation of MRP4 expression have not been investigated. In this study, we found that downregulation of ADAR1 increased the expression of MRP4 in human renal cells at the posttranscriptional level. Luciferase reporter assays and microarray analysis revealed that downregulation of ADAR1 reduced the levels of microRNA miR-381-3p, which led to the corresponding upregulation of MPR4 expression. Circular RNAs (circRNAs) are a type of closed-loop endogenous noncoding RNAs that play an essential role in gene expression by acting as miRNA sponges. We demonstrate that ADAR1 repressed the biogenesis of circRNA circHIPK3 through its adenosine-to-inosine RNA editing activity, which altered the secondary structure of the precursor of circHIPK3. Furthermore, in silico analysis suggested that circHIPK3 acts as a sponge of miR-381-3p. Indeed, we found overexpression of circHIPK3 induced the expression of MRP4 through its interference with miR-381-3p. Taken together, our study provides novel insights into regulation of the expression of xenobiotic transporters through circRNA expression by the RNA editing enzyme ADAR1.
| S-EPMC9293778 | biostudies-literature
Project description:Wild-type (WT) miR-378a-3p or edited miR-378a-3p were expressed in SB2 KD-ADAR1 cells to identify the genes regulated by edited miR-378a-3p vs WT miR-378a-3p. PARVA was one of the genes identified to be regulated by edited miR-378a-3p. We demonstrate that this regulation of PARVA is lost in highly metastatic melanoma cells. Microarray analysis was used to evaluate the robustness and reproducibility of the method used to generate the ex vivo tumor tissue model and confirm its ability to recapitulate the essential features of the original tumor.
2018-02-22 | GSE107088 | GEO
Project description:In order to confirm that circHIPK3 in colorectal cancerand characterization of its role in carcinogenesis, verified the expression level of circHIPK3 in additon 18 samples, and further collected 30 health controls and 30 colorectal cancer patients for exosome detection. The present study identified circHIPK3 is higher expression in CRC tissues and exosome of CRC patients.
2018-07-04 | GSE116589 | GEO
Project description:We profile gene expression upon circHIPK3 KD in two bladder cancer cell lines UMUC3 and J82
2021-10-01 | GSE148824 | GEO
Project description:Aberrant RNA-editing was observed in several human tumors, but its significance is mostly unknown. Here we show that ADAR1, a ubiquitous RNA-editing enzyme, is commonly lost in metastatic melanoma cells and specimens. Experimental ADAR1 silencing significantly alters melanoma cell morphology, facilitates proliferation and cell-cycle, and increases the tumorigenicity in-vivo. A series of ADAR1 truncation mutants establishes a novel RNA-editing-independent role for ADAR1 in controlling the nuclear and cytoplasmic processing steps of miRNA biogenesis. Altered expression of ADAR1-controled miRNAs accounts for the observed phenotype. We show that the oncogenic miR-17-5p endogenously regulates ADAR1 expression and that its genomic sequence is frequently amplified in melanoma to overexpress the mature miR-17-5p form. ADAR1 and miR-17-5p are ubiquitously expressed, suggesting the generality of this mechanism. Melanoma cell line expressing low ADAR1 levels (ADAR1-Knockdown) using shRNA technique were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to examine the alterations in the genes and microRNA expression profile in the manipulated cell system, due to ADAR1 possible involvement cancer development. To that end, we selected ADAR1-knockdown (ADAR1-KD) cells that demonstrated an enhanced aggressive phenotype both in vivo and in vitro as compared to the control cells (Control).
2012-08-31 | E-GEOD-31963 | biostudies-arrayexpress