Subcellular Localization of miRNAs and Implications in Cellular Homeostasis

Jie, Minwen; Feng, Tong; Huang, Wei; Zhang, Moran; Feng, Yuliang; Jiang, Hao; Wen, Zhiyuan

doi:10.3390/genes12060856

Cited by 35 publications

(30 citation statements)

References 111 publications

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“…We also It is well-studied that miRNAs are present in different cell organelles and cellular components such as the nucleus, mitochondria, Golgi bodies, exosomes and apoptotic bodies. These differentially expressed miRNAs, can modulate the levels of localized proteins 52 . Therefore, we hypothesized that synapsecentered miRNAs are altered in AD.…”

Section: Discussionmentioning

confidence: 99%

Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease

et al. 2022

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MicroRNAs (miRNAs) are found in nerve terminals, synaptic vesicles, and synaptosomes, but it is unclear whether synaptic and cytosolic miRNA populations differ in Alzheimer’s disease (AD) or if synaptosomal miRNAs affect AD synapse activity. To address these questions, we generated synaptosomes and cytosolic fractions from postmortem brains of AD and unaffected control (UC) samples and analyzed them using a global Affymetrix miRNAs microarray platform. A group of miRNAs significantly differed (P < 0.0001) with high fold changes variance (+/− >200-fold) in their expressions in different comparisons: (1) UC synaptosome vs UC cytosol, (2) AD synaptosomes vs AD cytosol, (3) AD cytosol vs UC cytosol, and (4) AD synaptosomes vs UC synaptosomes. MiRNAs data analysis revealed that some potential miRNAs were consistently different across sample groups. These differentially expressed miRNAs were further validated using AD postmortem brains, brains of APP transgenic (Tg2576), Tau transgenic (P301L), and wild-type mice. The miR-501-3p, miR-502-3p, and miR-877-5p were identified as potential synaptosomal miRNAs upregulated with disease progression based on AD Braak stages. Gene Ontology Enrichment and Ingenuity Pathway Analysis of synaptosomal miRNAs showed the involvement of miRNAs in nervous system development, cell junction organization, synapse assembly formation, and function of GABAergic synapse. This is the first description of synaptic versus cytosolic miRNAs in AD and their significance in synapse function.

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Section: Discussionmentioning

confidence: 99%

Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease

et al. 2022

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“…MiRNA is a small noncoding RNA of approximately 19–25 nucleotides in length and is highly conserved. It is involved in the early development and growth, proliferation, differentiation, division, and apoptosis of cells in various organisms; is involved in the regulation of important genes, humoral regulation, tissue reconstruction, endocrine regulation; and has important implications for the onset, development, and regression of disease [ 22 – 24 ]. MiRNAs have been extensively studied in osteoblast and osteoclast growth and differentiation.…”

Section: Discussionmentioning

confidence: 99%

Effect of miR-144-3p-Targeted Regulation of PTEN on Proliferation, Apoptosis, and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells under Stretch

Ling¹,

Luo

Lv³

et al. 2022

Emergency Medicine International

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Objective. To investigate the effects of miR-144-3p-targeted regulation of phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene on proliferation, apoptosis, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under retraction force. Methods. The BMSCs of rats were randomly divided into the tension MSC group with detrusor stimulation and the MSC group without detrusor stimulation, after which osteogenic differentiation of BMSCs was induced in both groups. Alkaline phosphatase (ALP) staining and alizarin red staining were used to detect the osteogenic differentiation ability of the two groups of cells. Real-time quantitative reverse transcription PCR (qRT-PCR) was used to detect the expression of miR-144-3p and PTEN in the two groups of cells after osteogenic differentiation. Bioinformatics website and dual luciferase reporter were used to detect the relationship between miR-144-3p and PTEN. The tension MSC group was used as a control group, and miR-144-3p mimics (miR-144-3p mimic group), mimic controls (mimic-NC group), PTEN interferers (si-PTEN group), and interference controls (si-NC group) were transfected into BMSCs. The BMSCs were then continuously stimulated for 24 h using a Flexercell in vitro cellular mechanics loading device, applying a draft force at a frequency of 1 Hz and a deformation rate of 18%. The cell proliferation was detected by Cell Counting Kit-8 (CCK-8) colorimetric assay; the expression levels of cyclin, cyclin-dependent kinases (CDK), BCL2-associated X (BAX), B-cell lymphoma-2 (BCL-2), and other cell cycle and apoptosis related proteins were detected by western blot (WB); and the osteogenic differentiation ability of MSC cells was detected by ALP staining and alizarin red staining. Results. Compared with the MSC group, the level of miR-144-3p was significantly lower and the level of PTEN was significantly higher in the tension MSC group. ALP staining showed normal activity in the MSC group and decreased ALP activity in the tension MSC group compared to the MSC group. Alizarin red staining in the MSC group showed scattered calcium nodule formation, and alizarin red staining showed red nodules with a more uniform color distribution. Compared to the MSC group, the tension MSC group showed fewer, smaller, and lighter staining mineralized nodules. Compared with the tension group and mimic-NC group (si-NC group), the proliferation rate of cells in the miR-144-3p mimic group (si-PTEN group) was significantly higher; the expression levels of PTEN and BAX were significantly lower; and the expression levels of cyclin, CDK, and BCL-2 protein were significantly higher. ALP staining results revealed that the miR-144-3p mimic group (si-PTEN group) showed significantly higher osteogenic differentiation ability and ALP activity of MSC than the tension group and mimic-NC group (si-NC group). Conclusion. miR-144-3p may inhibit apoptosis and promote proliferation and osteogenic differentiation of BMSCs under tension by targeting and regulating PTEN.

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“…They mediate post-transcriptional gene silencing by binding to target mRNAs, repressing their translation and/or promoting their degradation. Recently, miRNAs have also been found to act on promoters and enhancers to modulate gene expression [ 2 ]. Abnormal expression of miRNAs is implicated in the pathogenesis of several human diseases, such as cancer, as well as neurological, cardiovascular and metabolic diseases [ 3 , 4 ], indicating that a precise dosage and regulation are crucial for homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Small ORFs as New Regulators of Pri-miRNAs and miRNAs Expression in Human and Drosophila

Dozier

Montigny

Viladrich

et al. 2022

IJMS

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MicroRNAs (miRNAs) are small regulatory non-coding RNAs, resulting from the cleavage of long primary transcripts (pri-miRNAs) in the nucleus by the Microprocessor complex generating precursors (pre-miRNAs) that are then exported to the cytoplasm and processed into mature miRNAs. Some miRNAs are hosted in pri-miRNAs annotated as long non-coding RNAs (lncRNAs) and defined as MIRHGs (for miRNA Host Genes). However, several lnc pri-miRNAs contain translatable small open reading frames (smORFs). If smORFs present within lncRNAs can encode functional small peptides, they can also constitute cis-regulatory elements involved in lncRNA decay. Here, we investigated the possible involvement of smORFs in the regulation of lnc pri-miRNAs in Human and Drosophila, focusing on pri-miRNAs previously shown to contain translatable smORFs. We show that smORFs regulate the expression levels of human pri-miR-155 and pri-miR-497, and Drosophila pri-miR-8 and pri-miR-14, and also affect the expression and activity of their associated miRNAs. This smORF-dependent regulation is independent of the nucleotidic and amino acidic sequences of the smORFs and is sensitive to the ribosome-stalling drug cycloheximide, suggesting the involvement of translational events. This study identifies smORFs as new cis-acting elements involved in the regulation of pri-miRNAs and miRNAs expression, in both Human and Drosophila melanogaster.

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Subcellular Localization of miRNAs and Implications in Cellular Homeostasis

Cited by 35 publications

References 111 publications

Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease

Synaptosome microRNAs regulate synapse functions in Alzheimer’s disease

Effect of miR-144-3p-Targeted Regulation of PTEN on Proliferation, Apoptosis, and Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells under Stretch

Small ORFs as New Regulators of Pri-miRNAs and miRNAs Expression in Human and Drosophila

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