MiR-181a-5p mediates the effects of BMP4 on intestinal cell proliferation and differentiation
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ABSTRACT:
PROVIDER: PRJNA1251597 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR33167583.fastq.gz | Fastqsanger.gz | |||
| SRR33167585.fastq.gz | Fastqsanger.gz |
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Project description:The intestinal mucosa undergoes a dynamic process of continual proliferation, differentiation and apoptosis. Delineating the mechanisms involved in intestinal epithelial cell (IEC) differentiation is crucial to our understanding of not only normal gut adaptation but also aberrant intestinal growth. BMP signaling is a crucial regulator of intestinal proliferation and differentiation. However, the molecular underpinnings of the BMP pathway in this context are not entirely known. Here we showed a key role for BMP4/miR-181/glycolysis signaling pathway in the maintenance of intestinal epithelial cell proliferation and differentiation. Treatment with BMP4 increased expression of enterocyte markers and decreased proliferation of IECs, and importantly, decreased the expression of miR-181a-5p in mouse and human intestinal organoids. Inhibition of miR-181a-5p, a member of miR-181 with highest expression in intestinal cells, significantly increased enterocyte differentiation as noted by increased expression of enterocyte markers in human and mouse intestinal organoids. In addition, miR-181a-5p miRCURY LNA inhibitor repressed the expression of endogenous miR-181a-5p and decreased intestinal stem cell self-renewal as noted by the decreased expression of Ki67, cyclin D1 and OLFM4 and organoid forming efficiency. In contrast, overexpression of miR-181a-5p mimics decreased the expression of enterocyte markers. Moreover, BMP4 treatment or inhibition of miR-181a-5p repressed HK1 expression and inhibited glycolysis. In line of this, knockdown of HK1 or inhibition of glycolysis using 2-DG promoted enterocyte maturation and inhibited proliferation of IECs. Together, we provide evidence showing that miR-181a-5p inhibits intestinal enterocyte differentiation and promotes IEC proliferation thorough HK1-dependent glycolysis. Importantly, our findings identified miR-181a-5p as downstream in mediating BMP4 induction of enterocyte differentiation and inhibition of proliferation in IECs.
2025-04-30 | GSE266339 | GEO
Project description:The intestinal mucosa undergoes a dynamic process of continual proliferation, differentiation and apoptosis. Delineating the mechanisms involved in intestinal epithelial cell (IEC) differentiation is crucial to our understanding of not only normal gut adaptation but also aberrant intestinal growth. BMP signaling is a crucial regulator of intestinal proliferation and differentiation. However, the molecular underpinnings of the BMP pathway in this context are not entirely known. Here we showed that treatment with BMP4 increased expression of enterocyte markers and decreased proliferation of IECs, and importantly, decreased the expression of miR-181a-5p in mouse and human intestinal organoids. Inhibition of miR-181a-5p, a member of miR-181 with highest expression in intestinal cells, significantly increased enterocyte differentiation as noted by increased expression of enterocyte markers in human and mouse intestinal organoids. In addition, miR-181a-5p miRCURY LNA inhibitor repressed the expression of endogenous miR-181a-5p and decreased intestinal stem cell self-renewal as noted by the decreased expression of Ki67, cyclin D1 and OLFM4 and organoid forming efficiency. In contrast, overexpression of miR-181a-5p mimics decreased the expression of enterocyte markers. Together, we provide evidence showing that miR-181a-5p inhibits intestinal enterocyte differentiation and promotes IEC proliferation.
2025-06-04 | GSE294782 | GEO
Project description:miR-181a-5p mediates the effects of BMP4 on intestinal cell proliferation and differentiation
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Project description:Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor associated with poor prognosis. MicroRNAs (miRNAs) play crucial regulatory roles in the cancer development. However, the role of miRNAs in OSCC development and progression is not well understood. Methods: We sought to establish a dynamic Chinese hamster OSCC animal model, construct miRNA differential expression profiles of its occurrence and development, predict its targets, and perform functional analysis and validation in vitro. Results: Using expression and functional analyses, the key candidate miRNA (miR-181a-5p) was selected for further functional research, and the expression of miR-181a-5p in OSCC tissues and cell lines was detected. Subsequently, transfection technology and a nude mouse tumorigenic model were used to explore potential molecular mechanisms. miR-181a-5p was significantly downregulated in human OSCC specimens and cell lines, and decreased miR-181a-5p expression was observed in multiple stages of the Chinese hamster OSCC animal model. Moreover, upregulated miR-181a-5p significantly inhibited OSCC cell proliferation, colony formation, invasion, and migration; blocked the cell cycle; and promoted apoptosis. BCL2 was identified as a target of miR-181a-5p. BCL2 may interact with apoptosis- (BAX), invasion- and migration- (TIMP1, MMP2, and MMP9), and cell cycle-related genes (KI67, E2F1, CYCLIND1, and CDK6) to further regulate biological behavior. Tumor xenograft analysis indicated that tumor growth was significantly inhibited in the high miR-181a-5p expression group. Conclusions: Our findings indicate that miR-181a-5p can be used as a potential biomarker and provide a novel animal model for mechanistic research on oral cancer.
2023-01-10 | GSE222429 | GEO
Project description:Purpose: FOLFIRINOX has become standard therapy for patients with advanced stages pancreatic ductal adenocarcinoma (PDAC). However, only a subset of patients benefits from this therapy and biomarkers to guide clinical decisions are lacking. This study aimed to discover circulating microRNAs (miRNAs) as potential stratifying and monitoring biomarkers in patients with PDAC treated with FOLFIRINOX and to investigate their functional roles. Methods: A microarray was used in plasma samples from a first cohort of 11 patients selected based on their long versus short progression-free survival (PFS) after FOLFIRINOX. Nine miRNAs were validated using RT-qPCR in an independent cohort (n=43). The best discriminative miRNA was evaluated in tumor tissue samples and associated with clinicopathological features by Cox regression analyses. In vitro studies explored its role on cell proliferation, key downstream targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. Results: MiR-181a-5p was validated as significantly down-regulated in non-progressive compared to progressive patients after FOLFIRINOX. In multivariate analysis, this down-regulation correlated with improved PFS and overall survival, especially combined with CA19.9 decline (log-rank p<0.001, HR=0.153, 95% C.I. 0.067–0.347 and log-rank p=0.033, HR=0.201, 95% C.I. 0.070–0.576, respectively). Overexpression of miR-181a-5p increased proliferation of PDAC cells and inversely correlated with expression of ATM. Furthermore, inhibition of miR-181a-5p coupled with oxaliplatin exposure increased DNA damage and decreased cell viability. Conclusion: Our findings endorse miR-181a-5p as a biomarker for monitoring response to FOLFIRINOX and prognostication. MiR-181a-5p inhibition can potentially enhance sensitivity to oxaliplatin by amplifying the DNA damage response and cell death.
2019-01-01 | GSE109647 | GEO
Project description:Plasma from 245 patients with advanced NSCLC who received nivolumab as second-line therapy was collected and analyzed. EV-miRnome was profiled on 174/245 patients by microarray platform and selected EV-miRs were validated by qPCR. A prognostic model combining EV-miR and clinical variables was built using stepwise Cox regression analysis and tested on an independent patient cohort (71/245). EV-PD-L1 gene copy number was assessed by digital PCR. For 54 patients with disease control, EV-miR changes at best response versus baseline were investigated by microarray and validated by qPCR. EV-miRNome profiling at baseline identified two EV-miR (miR-181a-5p, miR-574-5p) that, combined with performance status, are capable of discriminating patients unlikely from those that are likely to benefit from immunotherapy (median overall survival of 4 months or higher than 9 months, respectively). EV-PD-L1 digital evaluation reported higher baseline copy number in patients at increased mortality risk, without improving the prognostic score. Best response EV-miRNome profiling selected six deregulated EV-miRs (miR19a-3p, miR-20a-5p, miR-142-3p, miR-1260a, miR-1260b, miR-5100) in responding patients. Their longitudinal monitoring highlighted a significant downmodulation already in the first treatment cycles, which lasted more than six months. Grantee: Simona Coco Grantor: Italian Ministry of Health Grant ID: CO-2016-02361470 Grant Title: Exosomal miRNA signature as prognostic marker in advanced non-small cell lung cancer (NSCLC) patients treated with Nivolumab
2024-07-28 | GSE207715 | GEO
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Project description:Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.Physical exercise stimulates adult hippocampal neurogenesis in mammals, and is considered a relevant strategy for preventing age-related cognitive decline in aging humans. However, its mechanism is controversial. Here, by investigating microRNAs (miRNAs) and their downstream pathways, we uncover that downregulation of miR-135a-5p mediates exercise-induced proliferation of adult NPCs in adult neurogenesis in the mouse hippocampus, likely by activation of phosphatidylinositol (IP3) signaling. Specifically, while overexpression of miR-135 prevents exercise-induced proliferation in the adult mouse hippocampus in vivo and in NPCs in vitro, its inhibition activates NPCs proliferation in resting and aged mice. Label free proteomics and bioinformatics analysis identifies 11 potential targets of miR-135 in NPCs, several of them involved in phosphatidylinositol signaling. Thus, miR-135a is key in mediating exercise-induced adult neurogenesis and opens intriguing perspectives toward the therapeutic exploitation of miR-135 to delay or prevent pathological brain ageing.
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Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by deep sequencing, using Illumina HiSeqTM 2500 platform Results: Using an optimized data analysis method, we mapped about 17 million sequence reads per sample. Differential analysis showed the expressions of 35 EV delivered miRNAs were significantly different between serum of patients with PCa and BPH, with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.
2020-01-31 | GSE134205 | GEO
Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by miRNA chip array, using Agilent-070156 Human_miRNA_V21.0_Microarray plateform. Results: Differential analysis showed the expressions of 27 EV delivered miRNAs were significantly different between serum of patients with bone-metastatic PCa and non-bone-metastatic PCa with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.
2020-01-31 | GSE134266 | GEO