MiR-106b-5p is a key player in adaptive response to drug-induced liver injury and liver regeneration by targeting vimentin
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE160961 | GEO | 2020/11/07
REPOSITORIES: GEO
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Project description:miR-106b-5p is a key player in adaptive response to drug-induced liver injury and liver regeneration by targeting vimentin
| PRJNA675003 | ENA
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: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: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.
2009-02-19 | GSE14831 | GEO
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: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 3M-bM-^@M-^YUTR 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. LNCaP cells were transfected with pre-miR oligos and 24 hr post-transfection total RNA was collected for microarray anaylsis.
2012-04-30 | E-GEOD-34893 | biostudies-arrayexpress
Project description:we assessed characteristic molecular and proteomic signatures in rat liver treated with drugs (pyrazinamide, ranitidine, enalapril, carbamazepine, and chlorpromazine) that are known to cause DILI in humans. In the present study, we assessed the characteristic gene expression signature for DILI in a rat model. Rats were administered representative drugs that are already known to induce DILI in humans and transcriptomic changes in rat liver were analyzed. The representative drugs, which induce three types (hepatocellular, mixed, and cholestatic) of DILI, that were used in this study were pyrazinamide (PZA, 150~1500 mg/kg), ranitidine (RAN, 209.5~2095 mg/kg), enalapril (ENA, 148.65~1486.5 mg/kg), carbamazepine (CBZ, 97.85~978.5 mg/kg), and chlorpromazine (CPZ, 7.1~71 mg/kg).
2013-08-16 | E-GEOD-49631 | biostudies-arrayexpress
Project description:Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury (DILI) and acute liver failure (ALF), and patients with advanced APAP toxicity rarely benefit from N-acetylcysteine (NAC), which is the first-line agent used in the clinic. Mesenchymal stromal cells (MSCs) and their extracellular vesicles (MSC-EVs) have shown promising effects in the treatment of DILI by decreasing neutrophil infiltration. However, the specific mechanism underlying the therapeutic effects of MSCs or MSC-EVs still needs to be elucidated. In this study, by using RNA-seq, we found that CXCL1, which is a chemoattractant for neutrophils, is a key molecule in MSC-mediated amelioration of DILI, and by luciferase reporter assay, we verified that MSC-EV-derived miR-186-5p binds to the 3’-UTR of CXCL1 to inhibit its expression in hepatocytes. Neutralizing CXCL1 reduces APAP-induced liver damage in vivo, and the agomir miR-186-5p shows excellent potential in the treatment of DILI. Overall, these findings suggest that the use of MSC-EVs may be a promising novel strategy for preventing DILI and that targeting the miR-186-5P/CXCL1 axis is a feasible approach for improving the efficacy of MSCs in the treatment of DILI.
2024-11-13 | GSE252192 | GEO
Project description:iPSCs were differentiated to human liver organoids as previously described. Human liver organoids were dispersed into single-cell suspension with trypsin (0.25%) and transferred to both channels in an dual-channel organ on chip system and cultured in hepatocyte maturation media. Media flow was regulated to 30 µL/hr for both channels. After 7 days of culture, liver chips were treated with vehicle control, or DILI-related compounds APAP, FIAU, tenofovir, or a tenofovir-inarigivir combination. scRNA sequencing was performed on intact HLOs and liver chips treated with each condition to compare HLOs pre- and post-chip and provide mechanistic DILI insight of treatments. Each sample generated between 440 and 860 million barcoded reads corresponding to an estimated 4,600 to 25,000 cells per sample
2022-01-24 | GSE188541 | GEO