miRNA Biogenesis and Function

Olena, Abigail F.; Patton, James G.

doi:10.1007/978-1-4899-8065-6_1

Cited by 3 publications

(4 citation statements)

References 173 publications

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“…A mature miRNA duplex with two strands that are each 21-22 nt long is produced in the cytoplasm by the processing of the pre-miRNA by Dicer and its cofactor TRBP. After that, the RNA-induced silencing complex (RISC) incorporates this miRNA duplex [25].…”

Section: Canonical Mirna Biogenesis and Functionsmentioning

confidence: 99%

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Functional Role of MicroRNAs in Embryogenesis

Babar Khawar,

Rasheed,

Afzal

et al. 2024

Genetics

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This book chapter will provide an overview of the functional role of microRNAs (miRNAs) in embryogenesis. A brief introduction to embryogenesis and emphasis on the importance of miRNAs in gene regulation will be provided. The biogenesis and mechanism of action of miRNAs will be discussed in detail with a focus on the importance of miRNA-mRNA interaction in gene regulation. The chapter will then delve into the role of miRNAs in early embryonic development, including their importance in the establishment of the three germ layers, cell proliferation, differentiation, and apoptosis during embryogenesis. The role of miRNAs in organogenesis and tissue differentiation, specifically the formation of specific organs such as the heart, lung, liver, and brain, will also be discussed. The chapter will conclude by examining the dysregulation of miRNAs in embryonic development and disease, including teratogenicity, developmental disorders, and developmental cancer. The chapter will summarize the functional roles of miRNAs in embryogenesis and will offer future perspectives and potential therapeutic applications of miRNAs in embryonic development and disease.

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Section: Canonical Mirna Biogenesis and Functionsmentioning

confidence: 99%

“…RNA Pol II produces the Dicer-independent miRNA miR-451, which is then processed by Drosha/DGCR8 and exported from the nucleus by Exp5. Argonaute 2 (Ago 2) binds to miR-451; once it is inside the cytoplasm, where it is then cut into the functional, mature, single-stranded miRNA [25].…”

Section: Noncanonical Mirnasmentioning

confidence: 99%

Functional Role of MicroRNAs in Embryogenesis

Babar Khawar,

Rasheed,

Afzal

et al. 2024

Genetics

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“…Curcumin and its derivative, like EF24, are known to regulate the epigenome by micro-RNAs(miRNA) expression ( 13 – 15 ). miRNAs,~22nt short non-coding RNAs, regulate gene expression by either blocking mRNA translation or degrading the mRNA using sequence complementarity ( 16 , 17 ). In cancer, dysregulation of miRNAs regulating various biological processes related to oncogenesis has been studied ( 18 , 19 ).…”

Section: Introductionmentioning

confidence: 99%

ST08 Altered NF-κB Pathway in Breast Cancer Cells In Vitro as Revealed by miRNA-mRNA Analysis and Enhanced the Effect of Cisplatin on Tumour Reduction in EAC Mouse Model

et al. 2022

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ST08 is a novel curcumin derivative that exhibited apoptotic and anti-migratory activity in MDA-MB-231, triple-negative breast cancer cells reported earlier. In this study, we further explored the anticancer properties of ST08. ST08 reduced tumor burden in vivo and induced apoptosis through the mitochondrial pathway both in vitro and in vivo. ST08 potentiated the effect of cisplatin in vitro and in vivo in mouse EAC breast cancer models with minimal toxicity. ST08 induced alterations in the gene expression were studied by parallel analysis of miRNA and mRNA. 74 differentially expressed miRNA regulated 114 mRNA in triple-negative (MDA-MB-231) cancer cells. Pathway related to the ECM was altered in mesenchymal MDA-MB-231 cells. We constructed a unique miRNA-mRNA interaction network, and one of the pathways regulated by miRNA was NF-κB. Targets of NF-κB like MMP1, PTX3, and MMP2 were downregulated in MDA-MB-231 in response to ST08 treatment. PMA induced cell proliferation was abrogated by ST08 treatment, and no additional cell cytotoxicity was observed when used in combination with IKK-16 indicating ST08 regulation of NF-κB pathway in MDA-MB-231 cells.

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“…Integrated RNA-seq and miRNA-seq approaches can effectively study drug-induced transcriptomic interactions. miRNAs are ~ 22 nt short non-coding RNAs that regulate gene expression by creating either a transcriptional or translational block leading to the absence of protein (9,10). Since a single miRNA can bind to 3' or 5' UTR of many genes, dysregulation of miRNAs can have a huge impact on cancer, a major cell signalling disorder.…”

Section: Introductionmentioning

confidence: 99%

Curcumin derivative 1,2-bis((3E,5E)-3,5-bis(4-chlorobenzylidene)-4-oxopiperidine-1- yl)ethane-1,2-dione hemihydrate, ST09, regulates miR-197-5p/GPX3 axis in breast cancer cells and abrogates tumor growth in mouse xenograft model

Nirgude

Desai

Ravindran

et al. 2022

Preprint

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Purpose: ST09, a potent curcumin derivative, exhibited apoptotic and anti-migratory activity in breast cancer cells in vitroand tumor reduction in vivo reported earlier. Here we aim to understand ST09 induced transcriptomic changes on regulation of the novel miR-197/GPX3 axis.We also aim to understand combinatory potential of ST09, anti-tumor efficacy in xenograft mice tumor model and its bioavailability studies. Methods: We performed mRNA-seq and miRNA-seq to capture the transcriptome of ST09 induced breast cancer cells. We used integrated approaches, to show regulation of miR-197/GPX3 axis via ST09. By performing luciferase assay and GPX activity assay, we confirm that GPX3 is one of the major targets of miR-197. We also showed anti-tumor effect ST09 on TNBC xenograft mice model. Phalloidin staining and wound healing assay were assayed to study migrastatic properties of ST09. The bioavailability studies of ST09 were also performed. Results:This study explored the global transcriptome profile of ST09 treated breast cancer cells (luminal and TNBC). The integrated approach revealed ST09 mediated regulation of a novel miRNA-mRNA axis, miR-197-5p/GPX3. Using GPX3 enzyme assay, we show the anti-proliferative role of GPX3 in breast cancer cells. We established GPX3 as a direct target of miR-197-5p. We show that ST09 potentiates the effect of cisplatin on breast cancer cells in vitro and reduces tumor burden in vivo with minimum toxicity. ST09 also showed a significant tumor reduction TNBC xenograft mice model. We show that the bioavailability of ST09 is 200X better than curcumin. Conclusion: ST09 is a potent curcumin derivative with a tumor-suppressive role. The integrated approach with the ST09 drug indicated the role of the miR-197-5p/GPX3 axis in breast cancer cells. ST09 upregulated GPX3 by repressing miR-197-5p and mediated the anti-proliferative effect in breast cancer cells. ST09 can be exploited either as a single chemotherapeutic agent or in combination treatment modalities, reducing the dosage of potent drugs.

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miRNA Biogenesis and Function

Cited by 3 publications

References 173 publications

Functional Role of MicroRNAs in Embryogenesis

Functional Role of MicroRNAs in Embryogenesis

ST08 Altered NF-κB Pathway in Breast Cancer Cells In Vitro as Revealed by miRNA-mRNA Analysis and Enhanced the Effect of Cisplatin on Tumour Reduction in EAC Mouse Model

Curcumin derivative 1,2-bis((3E,5E)-3,5-bis(4-chlorobenzylidene)-4-oxopiperidine-1- yl)ethane-1,2-dione hemihydrate, ST09, regulates miR-197-5p/GPX3 axis in breast cancer cells and abrogates tumor growth in mouse xenograft model

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