Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression of the miR-302/367 microRNA cluster is regulated by a conserved long non-coding host-gene.

ABSTRACT: MicroRNAs are important regulators of cellular functions. MiR-302/367 is a polycistronic miRNA cluster that can induce and maintain pluripotency. Here we investigate the transcriptional control and the processing of the miR-302 host-gene in mice. Our results indicate that the mmu-miR-302 host-gene is alternatively spliced, polyadenylated and exported from the nucleus. The regulatory sequences extend at least 2 kb upstream of the transcription start site and contain several conserved binding sites for both transcriptional activators and repressors. The gene structure and regulatory elements are highly conserved between mouse and human. So far, regulating miR-302 expression is the only known function of the miR-302 host-gene. Even though we here only provide one example, regulation of microRNA transcription might be a so far little recognized function of long non-coding RNA genes.

SUBMITTER: Rahimi K

PROVIDER: S-EPMC8159989 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Repression of TGF-? Signaling in Breast Cancer Cells by miR-302/367 Cluster.

Project description:Objective:Epigenetic alterations of the malignantly transformed cells have increasingly been regarded as an important event in the carcinogenic development. Induction of some miRNAs such as miR-302/367 cluster has been shown to induce reprogramming of breast cancer cells and exert a tumor suppressive role by induction of mesenchymal to epithelial transition, apoptosis and a lower proliferation rate. Here, we aimed to investigate the impact of miR-302/367 overexpression on transforming growth factor-beta (TGF-?) signaling and how this may contribute to tumor suppressive effects of miR-302/367 cluster. Materials and Methods:In this experimental study, MDA-MB-231 and SK-BR-3 breast cancer cells were cultured and transfected with miR-302/367 expressing lentivector. The impact of miR-302/367 overexpression on several mediators of TGF-? signaling and cell cycle was assessed by quantitative real-time polymerase chain reaction (qPCR) and flow cytometry. Results:Ectopic expression of miR-302/367 cluster downregulated expression of some downstream elements of TGF-? pathway in MDA-MB-231 and SK-BR-3 breast cancer cell lines. Overexpression of miR-302/367 cluster inhibited proliferation of the breast cancer cells by suppressing the S-phase of cell cycle which was in accordance with inhibition of TGF-? pathway. Conclusion:TGF-? signaling is one of the key pathways in tumor progression and a general suppression of TGF-? mediators by the pleiotropically acting miR-302/367 cluster may be one of the important reasons for its anti-tumor effects in breast cancer cells.

| S-EPMC6722449 | biostudies-literature

MicroRNA-302/367 Cluster Impacts Host Antimicrobial Defense via Regulation of Mitophagic Response Against <i>Pseudomonas aeruginosa</i> Infection.

Project description:Mitophagy has recently been implicated in bacterial infection but the underlying mechanism remains largely unknown. Here, we uncover a role of microRNA-302/367 cluster in regulating mitophagy and its associated host response against bacterial infection. We demonstrate that miR-302/367 cluster expression was significantly increased after Pseudomonas aeruginosa infection. Enhanced expression of miR-302/367 cluster accelerated the mitophagic response in macrophages, thus increasing clearance of invading P. aeruginosa by regulating production of reactive oxygen species (ROS), while application of miR-302/367 cluster inhibitors decreased bacterial clearance. Blocking mitophagy with siRNA against mitophagy receptor prohibitin 2 (PHB2) reduced the effect of miR-302/367 cluster on induction of mitophagy and its-associated P. aeruginosa elimination. In addition, we found that miR-302/367 cluster also increased bacterial clearance in mouse model. Mechanistically, we illustrate that miR-302/367 cluster binds to the 3'-untranslated region of nuclear factor kappa B (NF-κB), a negative regulator of mitophagy, accelerated the process of mitophagy by inhibiting NF-κB. Furthermore, inhibition of NF-κB in macrophages attenuated the ROS or cytokines production and may reduce cell injury by P. aeruginosa infection to maintain cellular homeostasis. Collectively, our findings elucidate that miR-302/367 cluster functions as potent regulators in mitophagy-mediated P. aeruginosa elimination and pinpoint an unexpected functional link between miRNAs and mitophagy.

| S-EPMC7576609 | biostudies-literature

MicroRNA cluster 302-367 enhances somatic cell reprogramming by accelerating a mesenchymal-to-epithelial transition.

Project description:MicroRNAs (miRNAs) are emerging critical regulators of cell function that frequently reside in clusters throughout the genome. They influence a myriad of cell functions, including the generation of induced pluripotent stem cells, also termed reprogramming. Here, we have successfully delivered entire miRNA clusters into reprogramming fibroblasts using retroviral vectors. This strategy avoids caveats associated with transient transfection of chemically synthesized miRNA mimics. Overexpression of 2 miRNA clusters, 106a-363 and in particular 302-367, allowed potent increases in induced pluripotent stem cell generation efficiency in mouse fibroblasts using 3 exogenous factors (Sox2, Klf4, and Oct4). Pathway analysis highlighted potential relevant effectors, including mesenchymal-to-epithelial transition, cell cycle, and epigenetic regulators. Further study showed that miRNA cluster 302-367 targeted TGF? receptor 2, promoted increased E-cadherin expression, and accelerated mesenchymal-to-epithelial changes necessary for colony formation. Our work thus provides an interesting alternative for improving reprogramming using miRNAs and adds new evidence for the emerging relationship between pluripotency and the epithelial phenotype.

| S-EPMC3089577 | biostudies-literature

MicroRNA-302/367 cluster governs hESC self-renewal by dually regulating cell cycle and apoptosis pathways.

Project description:miR-302/367 is the most abundant miRNA cluster in human embryonic stem cells (hESCs) and can promote somatic cell reprogramming. However, its role in hESCs remains poorly understood. Here, we studied functional roles of the endogenous miR-302/367 cluster in hESCs by employing specific TALE-based transcriptional repressors. We revealed that miR-302/367 cluster dually regulates hESC cell cycle and apoptosis in dose-dependent manner. Gene profiling and functional studies identified key targets of the miR-302/367 cluster in regulating hESC self-renewal and apoptosis. We demonstrate that in addition to its role in cell cycle regulation, miR-302/367 cluster conquers apoptosis by downregulating BNIP3L/Nix (a BH3-only proapoptotic factor) and upregulating BCL-xL expression. Furthermore, we show that butyrate, a natural compound, upregulates miR-302/367 cluster expression and alleviates hESCs from apoptosis induced by knockdown of miR-302/367 cluster. In summary, our findings provide new insights in molecular mechanisms of how miR-302/367 cluster regulates hESCs.

| S-EPMC4400607 | biostudies-literature

Dissecting the roles of miR-302/367 cluster in cellular reprogramming using TALE-based repressor and TALEN.

Project description:MicroRNAs are important gene regulators involved in many biological processes, including stemness maintenance and cellular reprogramming. Current methods used in loss-of-function studies of microRNAs mainly include locked nucleic acid (LNA) oligonucleotides and miRZip inhibitors, which have several limitations. Due to their unique gene structures and small sizes, there is no efficient or simple strategy to knock down or knock out microRNAs or whole microRNA clusters. Here, we demonstrate knockdown of the miR-302/367 cluster by using the Kruppel-associated box repressor domain fused with specific transcription activator-like effectors (TALEs) designed to bind the miR-302/367 cluster promoter. We also designed two pairs of TALE nucleases (TALENs) to efficiently delete the miR-302/367 cluster in primary human fibroblasts and determined that knockout of the miR-302/367 cluster completely blocked induced pluripotent stem cell (iPSC) generation. Together, our results demonstrate that TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA clusters in somatic cells and pluripotent stem cells.

| S-EPMC3849252 | biostudies-literature

Expression data of reprogrammed miR-302/367-iPS cells

Project description:Pluripotent marker correlation between miR-302/367-iPS, ES and fibroblast cells

2011-05-01 | GSE27814 | GEO

Cell-based therapy using miR-302-367 expressing cells represses glioblastoma growth.

Project description:Glioblastomas are incurable primary brain tumors that affect patients of all ages. The aggressiveness of this cancer has been attributed in part to the persistence of treatment-resistant glioblastoma stem-like cells. We have previously discovered the tumor-suppressor properties of the microRNA cluster miR-302-367, representing a potential treatment for glioblastoma. Here, we attempted to develop a cell-based therapy by taking advantage of the capability of glioma cells to secrete exosomes that enclose small RNA molecules. We engineered primary glioma cells to stably express the miR-302-367. Remarkably, these cells altered, in a paracrine-dependent manner, the expression of stemness markers, the proliferation and the tumorigenicity of neighboring glioblastoma cells. Further characterization of the secretome derived from miR-302-367 expressing cells showed that a large amount of miR-302-367 was enclosed in exosomes, which were internalized by the neighboring glioblastoma cells. This miR-302-367 cell-to-cell transfer resulted in the inhibition of its targets such as CXCR4/SDF1, SHH, cyclin D, cyclin A and E2F1. Orthotopic xenograft of miR-302-367-expressing cells together with glioblastoma stem-like cells efficiently altered the tumor development in mice brain.

| S-EPMC5386523 | biostudies-literature

Sodium butyrate facilitates reprogramming by derepressing OCT4 transactivity at the promoter of embryonic stem cell-specific miR-302/367 cluster.

Project description:Small-molecule inhibitors and microRNAs (miRNAs) are two newly emerging classes of tools for optimizing induced pluripotent stem cell (iPSC) generation. We report here that sodium butyrate (NaB), a small-molecule inhibitor of histone deacetylases (HDACs), upregulates transcriptional levels of the miR-302/367 cluster by enhancing Oct4 transcriptional activity at the miR-302/367 cluster promoter. NaB does not affect the OCT4 DNA-binding domain; instead it enhances transactivity of the OCT4 transactivation domains. We elucidate that OCT4 transcriptional activity is usually dampened by its associated HDACs in cells and can be derepressed by NaB by impairing the interaction between Oct4 and HDACs, which leads to an elevated expression of the miR-302/367 cluster. Our new findings suggest a novel molecular mechanism for NaB in promoting somatic cell reprogramming via the miR-302/367 cluster.

| S-EPMC3967376 | biostudies-literature

Expression of the miR-302/367 cluster in glioblastoma cells suppresses tumorigenic gene expression patterns and abolishes transformation related phenotypes.

Project description:Cellular transformation is initiated by the activation of oncogenes and a closely associated developmental reprogramming of the epigenetic landscape. Transcription factors, regulators of chromatin states and microRNAs influence cell fates in development and stabilize the phenotypes of normal, differentiated cells and of cancer cells. The miR-302/367 cluster, predominantly expressed in human embryonic stem cells (hESs), can promote the cellular reprogramming of human and mouse cells and contribute to the generation of iPSC. We have used the epigenetic reprogramming potential of the miR-302/367 cluster to "de-program" tumor cells, that is, hift their gene expression pattern towards an alternative program associated with more benign cellular phenotypes. Induction of the miR-302/367 cluster in extensively mutated U87MG glioblastoma cells drastically suppressed the expression of transformation related proteins, for example, the reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC, and the transcription factors POU3F2, SALL2 and OLIG2, required for the maintenance of glioblastoma stem-like tumor propagating cells. It also diminished PI3K/AKT and STAT3 signaling, impeded colony formation in soft agar and cell migration and suppressed pro-inflammatory cytokine secretion. At the same time, the miR-302/367 cluster restored the expression of neuronal markers of differentiation. Most notably, miR-302/367 cluster expressing cells lose their ability to form tumors and to establish liver metastasis in nude mice. The induction of the miR-302/367 cluster in U87MG glioblastoma cells suppresses the expression of multiple transformation related genes, abolishes the tumor and metastasis formation potential of these cells and can potentially become a new approach for cancer therapy.

| S-EPMC4744715 | biostudies-literature

miR-302-367 regulates cardiomycyte proliferation and differentiation during development

Project description:To define the role of miR-302-367 cluster in cardiac development, we overexpressed miR-302-367 cluster in mouse heart by using R26R-miR-302-367; Nkx2.5-Cre mice. This data set contains the microarrays examining gene expression in the hearts of R26R-miR-302-367; Nkx2.5-Cre mice at postnatal day 14.

2015-01-01 | GSE54988 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data