MiR-106b-5p is a key player in adaptive response to drug-induced liver injury and liver regeneration by targeting vimentin
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA675003 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The key exosomal miRNAs in adaptive response to drug-induced liver (DILI) and liver regeneration were investigated and proved. This study aimed to decipher the mechanism of restorative events in the adaptive response to DILI by investigating circulating exosomal miRNAs. Using toosendanin-induced liver injury model, exosomal miR-106b-5p was identified as a robust driver in the adaptive response of TILI.
2020-11-07 | GSE160961 | GEO
Project description:Myocardial regeneration is restricted to early postnatal life, when mammalian cardiomyocytes still retain the ability to proliferate. The molecular cues that induce cell cycle arrest of neonatal cardiomyocytes towards terminally differentiated adult heart muscle cells remain obscure. We report that the miR-106b~25cluster is higher expressed in the early postnatal myocardium and decreases in expression towards adulthood, especially under conditions of overload, and orchestrates the transition of cardiomyocyte hyperplasia towards cell cycle arrest and hypertrophy by virtue of its targetome. To identify the relevant targets of individual miRNAs in the miR-106b~15 cluster and elucidate the molecular mechanisms underlying the proliferative effects of this microRNA cluster, we assessed the global transcriptomic changes by deep-sequencing total neonatal mouse cardiomyocyte RNA after exogeneous transfection with hsa-miR-106b-5p, hsa-miR-93-5p, hsa-miR-25-3p and compared the transcriptomic profiles to cardiomyocytes transfected with cel-miR-67, a control miRNA.
2021-06-25 | GSE178867 | GEO
Project description:Macrophage Secretion of miR-106b-5p Causes Renin-Dependent Hypertension
| PRJNA649967 | ENA
Project description:Understanding the endogenous mechanism of adaptive response to drug-induced liver injury (arDILI) may discover innovative strategies to manage DILI. To gain mechanistic insight into arDILI, we investigated exosomal miRNAs in the adaptive response to toosendanin-induced liver injury (TILI) of mice. Exosomal miR-106b-5p was identified as a specific regulator of arDILI by comprehensive miRNA profiling. Outstandingly, miR-106b-5p agomir treatment alleviated TILI and other DILI by inhibiting apoptosis and promoting hepatocyte proliferation. Conversely, antagomir treatments had opposite effects, indicating that miR-106b-5p protects mice from liver injury. Injured hepatocytes released miR-106b-5p-enriched exosomes taken up by surrounding hepatocytes. Vim (encodes vimentin) was identified as an important target of miR-106b-5p by dual luciferase reporter and siRNA assays. Furthermore, single-cell RNA-sequencing analysis of toosendanin-injured mouse liver revealed a cluster of Vim + hepatocytes; nonetheless declined following miR-106b-5p cotreatment. More importantly, Vim knockout protected mice from acetaminophen poisoning and TILI. In the clinic, serum miR-106b-5p expression levels correlated with the severity of DILI. Indeed, liver biopsies of clinical cases exposed to different DILI causing drugs revealed marked vimentin expression among harmed hepatocytes, confirming clinical relevance. Together, we report mechanisms of arDILI whereby miR-106b-5p safeguards restorative tissue repair by targeting vimentin.
| S-EPMC11337467 | biostudies-literature
Project description:microRNAs in the miR-106b family are overexpressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain of function promotes cell cycle progression, whereas loss of function reverses this phenotype. Microarray profiling uncovers multiple targets of the family, including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and that its silencing plays a key role in miR-106b-induced cell cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions. HCT116 Dicerex5 cells were transfected with microRNAs in six-well plates, and RNA was isolated 10 h after transfection. Transcripts containing the miR-106b family hexamers in their 3' UTRs were identified. By microarray analysis, 103 transcripts that contained miR-106b family complementary hexamers in their 3' UTRs were down-regulated by miR-106b, miR-106a, miR-20b, and miR-17-5p within 10 h of transfection.
2010-06-23 | E-GEOD-14831 | biostudies-arrayexpress
Project description:Adult beta cells in the pancreas are the sole source of insulin in our body. Beta cell loss or increased demand for insulin, impose metabolic challenges because adult beta cells are generally quiescent and infrequently re-enter the cell division cycle. miR-17-92/106b is a family of proto-oncogene microRNAs, that regulate proliferation in normal tissues and in cancer. Here, we employ mouse genetics to demonstrate a critical role for miR-17-92/106b in glucose homeostasis and in controlling insulin secretion. Mass spectrometry analysis was performed on miR-17-92LoxP/LoxP;106-25-/- MEF lysate, without or with CRE-Adenovirus. miR-17-92LoxP/LoxP;106-25+/+ MEFs with GFP-Adenovirus served as controls. We demonstrate that miR-17-92/106b regulate the adult beta cell mitotic checkpoint and that miR-17-92/106b deficiency results in reduction in beta cell mass in-vivo. Furthermore, protein kinase A (PKA) is a new relevant molecular pathway downstream of miR-17-92/106b in control of adult beta cell division and glucose homeostasis. Therefore, contributes to the understanding of proto-oncogene miRNAs in the normal, untransformed endocrine pancreas, and illustrates new genetic means for regulation of beta cell mitosis and function by non-coding RNAs.
2019-06-17 | PXD012610 | Pride
Project description:A unique feature of the liver is its high regenerative capacity, which is essential to maintain liver homeostasis. However, key regulators of liver regeneration (LR) remain ill-defined. Here, we identify hepatic miR-182-5p as a key regulator of LR. Suppressing miR-182-5p, whose expression is significantly induced in the liver of mice post two-thirds partial hepatectomy (PH), abrogates PH-induced LR in mice. In contrast, liver-specific overexpression of miR-182-5p promotes LR in mice with PH. Overexpression of miR-182-5p failed to promote proliferation in hepatocytes, but stimulates proliferation when hepatocytes are cocultured with stellate cells. Mechanistically, miR-182-5p stimulates Cyp7a1-mediated cholic acid production in hepatocytes, which promotes hedgehog (Hh) ligand production in stellate cells, leading to the activation of Hh signaling in hepatocytes and consequent cell proliferation. Collectively, our study identified miR-182-5p as a critical regulator of LR and uncovers a Cyp7a1/cholic acid-dependent mechanism by which hepatocytes crosstalk to stellate cells to facilitate LR.
2022-08-10 | GSE206451 | GEO
Project description:Rationale：Poor peri-implant osseointegration of dental implants in patients with type II diabetes has become a major clinical challenge in recent years. MSC (Mesenchymal stem cell)-derived exosomes may play an important role in peri-implant osseointegration, but the mechanism remains unclear. Enhancing the therapeutic effect of MSC-derived exosomes and exploring the potential mechanism can help provide a new therapeutic strategy to improve the clinical outcome of dental implant restorations in patients with type II diabetes. Methods：The exosomes derived from hypoxia (Hypo-exos) or normoxia (Nor-exos) preconditioned bone marrow mesenchymal stem cells (BMSCs) were co-cultured with BMSCs and human umbilical vein endothelial cells (HUVECs). The effect of exosomes on BMSCs cell proliferation was detected by CCK-8 assay and EdU assay, and the effect on angiogenesis ability of HUVECs was detected by wound healing assay, transwell migration assay, tube formation assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A diabetic rat dental implant model was also established and the effect of exosomes on implant osseointegration was evaluated through micro-CT scanning and histological analysis. The differentially expressed miRNAs between Hypo-exos and Nor-exos were identified by high-throughput miRNA sequencing. Subsequently, the target genes and their roles in regulating angiogenesis were predicted and analyzed by bioinformatics analysis and dual luciferase reporter assay. Results：In vitro experiments indicated that hypoxia preconditioning could elevate exosome production and promote cell proliferation of BMSCs and angiogenesis of HUVECs. Moreover, Hypo-exos promoted peri-implant osteogenesis in rats with diabetes. Further investigation revealed the vital involvement of the miR-106b-5p/HIF-1α axis in promoting peri-implant osseointegration. Conclusion: Exosomes derived from hypoxia-preconditioned BMSCs could improve the peri-implant osseointegration in rats with diabetes by promoting cell proliferation and angiogenesis, and the miR-106b-5p/ HIF-1α axis could be the underlying mechanism.
2024-09-04 | GSE275863 | GEO
Project description:We and others previously reported that the miR-106b-25 microRNA cluster is a candidate oncogene in human prostate cancer. Here, we made the novel observation that miR-106b-25 expression is further up-regulated in distant metastasis. Moreover, increased tumor miR-106b expression was associated with early disease recurrence. To identify yet unknown oncogenic functions of the prognostic miR-106b, we overexpressed it in LNCaP human prostate cancer cells to examine miR-106b-induced global expression changes among protein-coding genes. The approach revealed that caspase-7 is a candidate direct target of miR-106b, which was confirmed by Western blot analysis and a 3’UTR reporter assay. Other analyses showed that caspase-7 is down-regulated in primary human prostate tumors and metastatic lesions across multiple datasets and is by itself associated with disease recurrence. Using bioinformatics, we also discovered that miR-106b-25 may specifically influence focal adhesion-related pathways. This observation was experimentally confirmed using miR-106b-25-transduced 22Rv1 human prostate cancer cells. After infection with a miR-106b-25 lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane- and bone matrix-related filaments and enhanced soft agar growth. In summary, miR-106b-25 was found to be associated with prostate cancer progression and metastasis and may do so by altering apoptosis- and focal adhesion-related pathways. To elucidate the effects miR-106b, we up-regulated miR-106b in LNCaP cells and examined gene expression alterations on a global scale with Affymetrix arrays.
2012-05-01 | GSE34893 | GEO
Project description:RNA-seq profiles of rat cardiomyocytes overexpressing hsa-miR-106b-5p, hsa-miR-93-5p, hsa-miR-25-3p or cel-miR-67
| PRJNA741260 | ENA