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Molecular Medicine Reports May 2024Recurrent miscarriage is used to refer to more than three pregnancy failures before 20 weeks of gestation. Defective trophoblast cell growth and invasion are frequently...
Recurrent miscarriage is used to refer to more than three pregnancy failures before 20 weeks of gestation. Defective trophoblast cell growth and invasion are frequently observed in recurrent miscarriage. Several microRNAs (miRs), including miR‑155‑5p, are aberrantly upregulated in recurrent miscarriage; however, the underlying molecular mechanisms remain unclear. The centrosome orchestrates microtubule networks and coordinates cell cycle progression. In addition, it is a base for primary cilia, which are antenna‑like organelles that coordinate signaling during development and growth. Thus, deficiencies in centrosomal functions can lead to several disease, such as breast cancer and microcephaly. In the present study, the signaling cascades were analyzed by western blotting, and the centrosome and primary cilia were observed and analyzed by immunofluorescence staining. The results showed that overexpression of miR‑155‑5p induced centrosome amplification and blocked primary cilia formation in trophoblast cells. Notably, centrosome amplification inhibited trophoblast cell growth by upregulating apoptotic cleaved‑caspase 3 and cleaved‑poly (ADP‑ribose) polymerase in miR‑155‑5p‑overexpressing trophoblast cells. In addition, overexpression of miR‑155‑5p inhibited primary cilia formation, thereby inhibiting epithelial‑mesenchymal transition and trophoblast cell invasion. All phenotypes could be rescued when cells were co‑transfected with the miR‑155‑5p inhibitor, thus supporting the role of miR‑155‑5p in centrosomal functions. It was also found that miR‑155‑5p activated autophagy, whereas disruption of autophagy via the depletion of autophagy‑related 16‑like 1 alleviated miR‑155‑5p‑induced apoptosis and restored trophoblast cell invasion. In conclusion, the present study indicated a novel role of miR‑55‑5p in mediating centrosomal function in recurrent miscarriage.
Topics: Pregnancy; Female; Humans; MicroRNAs; Trophoblasts; Cell Proliferation; Centrosome; Cell Movement; Abortion, Habitual
PubMed: 38551159
DOI: 10.3892/mmr.2024.13209 -
International Journal of Molecular... Dec 2019MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves... (Review)
Review
MicroRNAs (miRNAs) are approximately 22-nucleotide-long, small non-coding RNAs that post-transcriptionally regulate gene expression. The biogenesis of miRNAs involves multiple steps, including the transcription of primary miRNAs (pri-miRNAs), nuclear Drosha-mediated processing, cytoplasmic Dicer-mediated processing, and loading onto Argonaute (Ago) proteins. Further, miRNAs control diverse biological and pathological processes via the silencing of target mRNAs. This review summarizes recent findings regarding the quantitative aspects of miRNA homeostasis, including Drosha-mediated pri-miRNA processing, Ago-mediated asymmetric miRNA strand selection, and modifications of miRNA pathway components, as well as the roles of RNA modifications (epitranscriptomics), epigenetics, transcription factor circuits, and super-enhancers in miRNA regulation. These recent advances have facilitated a system-level understanding of miRNA networks, as well as the improvement of RNAi performance for both gene-specific targeting and genome-wide screening. The comprehensive understanding and modeling of miRNA biogenesis and function have been applied to the design of synthetic gene circuits. In addition, the relationships between miRNA genes and super-enhancers provide the molecular basis for the highly biased cell type-specific expression patterns of miRNAs and the evolution of miRNA-target connections, while highlighting the importance of alterations of super-enhancer-associated miRNAs in a variety of human diseases.
Topics: Animals; Argonaute Proteins; Humans; MicroRNAs; RNA, Messenger; Synthetic Biology
PubMed: 31878193
DOI: 10.3390/ijms21010132 -
RNA Biology Jan 2024MicroRNAs are a class of small regulatory RNAs that mediate regulation of protein synthesis by recognizing sequence elements in mRNAs. MicroRNAs are processed through a... (Review)
Review
MicroRNAs are a class of small regulatory RNAs that mediate regulation of protein synthesis by recognizing sequence elements in mRNAs. MicroRNAs are processed through a series of steps starting from transcription and primary processing in the nucleus to precursor processing and mature function in the cytoplasm. It is also in the cytoplasm where levels of mature microRNAs can be modulated through decay mechanisms. Here, we review the recent progress in the lifetime of a microRNA at all steps required for maintaining their homoeostasis. The increasing knowledge about microRNA regulation upholds great promise as therapeutic targets.
Topics: MicroRNAs; RNA, Messenger; Protein Biosynthesis; Ribonuclease III
PubMed: 38031325
DOI: 10.1080/15476286.2023.2288741 -
Reviews in Endocrine & Metabolic... Jun 2022Extracellular vesicles (EVs) are small anuclear vesicles, delimited by a lipid bilayer, released by almost all cell types, carrying functionally active biological... (Review)
Review
Extracellular vesicles (EVs) are small anuclear vesicles, delimited by a lipid bilayer, released by almost all cell types, carrying functionally active biological molecules that can be transferred to the neighbouring or distant cells, inducing phenotypical and functional changes, relevant in various physio-pathological conditions. The microRNAs are the most significant active components transported by EVs, with crucial role in intercellular communication and significant effects on recipient cells. They may also server as novel valuable biomarkers for the diagnosis of metabolic disorders. Moreover, EVs are supposed to mediate type 2 diabetes mellitus (T2DM) risk and its progress. The T2DM development is preceded by prediabetes, a state that is associated with early forms of nephropathy and neuropathy, chronic kidney disease, diabetic retinopathy, and increased risk of macrovascular disease. Although the interest of scientists was focused not only on the pathogenesis of diabetes, but also on the early diagnosis, little is known about EVs-incorporated microRNA involvement in prediabetes state and its microvascular and macrovascular complications. Here, we survey the biogenesis, classification, content, biological functions and the most popular primary isolation methods of EVs, review the EVs-associated microRNA profiling connexion with early stages of diabetes and discuss the role of EVs containing specific microRNAs in prediabetes complications.
Topics: Biomarkers; Diabetes Mellitus, Type 2; Extracellular Vesicles; Humans; MicroRNAs; Prediabetic State
PubMed: 34143360
DOI: 10.1007/s11154-021-09664-y -
Pathology, Research and Practice Sep 2023Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as... (Review)
Review
Cancer is a complex genetic anomaly involving coding and non-coding transcript structural and expressive irregularities. A class of tiny non-coding RNAs known as microRNAs (miRNAs) regulates gene expression at the post-transcriptional level by binding only to messenger RNAs (mRNAs). Due to their capacity to target numerous genes, miRNAs have the potential to play a significant role in the development of tumors by controlling several biological processes, including angiogenesis, drug resistance, metastasis, apoptosis, proliferation, and drug resistance. According to several recent studies, miRNA-214 has been linked to the emergence and spread of tumors. The human genome's q24.3 arm contains the DNM3 gene, which is about 6 kb away and includes the microRNA-214. Its primary purpose was the induction of apoptosis in cancerous cells. The multifaceted and complex functions of miR-214 as a modulator in neoplastic conditions have been outlined in the current review.
Topics: Humans; Neoplasms; MicroRNAs; Apoptosis; RNA, Messenger
PubMed: 37660658
DOI: 10.1016/j.prp.2023.154770 -
Nucleic Acids Research Sep 2017Changes in mature microRNA (miRNA) levels that occur downstream of signaling cascades play an important role during human development and disease. However, the...
Changes in mature microRNA (miRNA) levels that occur downstream of signaling cascades play an important role during human development and disease. However, the regulation of primary microRNA (pri-miRNA) genes remains to be dissected in detail. To address this, we followed a data-driven approach and developed a transcript identification, validation and quantification pipeline for characterizing the regulatory domains of pri-miRNAs. Integration of 92 nascent transcriptomes and multilevel data from cells arising from ecto-, endo- and mesoderm lineages reveals cell type-specific expression patterns, allows fine-resolution mapping of transcription start sites (TSS) and identification of candidate regulatory regions. We show that inter- and intragenic pri-miRNA transcripts span vast genomic regions and active TSS locations differ across cell types, exemplified by the mir-29a∼29b-1, mir-100∼let-7a-2∼125b-1 and miR-221∼222 clusters. Considering the presence of multiple TSS as an important regulatory feature at miRNA loci, we developed a strategy to quantify differential TSS usage. We demonstrate that the TSS activities associate with cell type-specific super-enhancers, differential stimulus responsiveness and higher-order chromatin structure. These results pave the way for building detailed regulatory maps of miRNA loci.
Topics: Cell Line; Cell Line, Tumor; Cell Lineage; Chromatin; Chromosome Mapping; Ectoderm; Endoderm; Gene Expression Regulation, Developmental; Genetic Loci; Humans; Mesoderm; MicroRNAs; Molecular Sequence Annotation; Multigene Family; Organ Specificity; Promoter Regions, Genetic; Transcription Initiation Site; Transcriptome
PubMed: 28973462
DOI: 10.1093/nar/gkx680 -
Cell and Tissue Research Jun 2014Aberrant DNA methylation of regulatory sequences is a well-documented mechanism of functional deletion of genes with anti-tumourigenic properties including microRNAs.... (Review)
Review
Aberrant DNA methylation of regulatory sequences is a well-documented mechanism of functional deletion of genes with anti-tumourigenic properties including microRNAs. This review discusses the publications describing aberrant methylation of microRNA genes in human breast cancer cells. Among the anti-tumourigenic properties of epigenetically inactivated microRNA genes, the inhibition of proliferation and of epithelial-to-mesenchymal transition (EMT) are the best studied. Several studies are conceptually very interesting and present a comprehensive functional characterization of anti-tumorigenic microRNAs. The link between microRNA expression and gene methylation is not addressed directly by all studies and a number of studies are limited in their strength by not including primary breast cancer specimens or by analysing very small sets of primary human specimens. The publications cover a wide range of DNA methylation detection techniques, often making direct comparison of results challenging. Despite the identification and thorough characterization of many interesting candidates and functionally important microRNA genes affected by DNA methylation, the translation of microRNA gene methylation as a new biomarker into the daily routine practice has not yet worked out.
Topics: Breast Neoplasms; DNA Methylation; DNA, Neoplasm; Epithelial-Mesenchymal Transition; Female; Humans; MicroRNAs; RNA, Neoplasm
PubMed: 24509818
DOI: 10.1007/s00441-014-1793-0 -
Journal of Bone and Mineral Metabolism May 2023Bone metastasis is a common complication in several solid cancers, including breast, prostate, and lung. In the bone microenvironment, metastatic cancer cells disturb... (Review)
Review
Bone metastasis is a common complication in several solid cancers, including breast, prostate, and lung. In the bone microenvironment, metastatic cancer cells disturb bone homeostasis leading to osteolytic or osteosclerotic lesions. Osteolytic lesions are characterized by an increased osteoclast-mediated bone resorption while osteosclerotic lesions are caused by enhanced activity of osteoblasts and formation of poor-quality bone. A common feature in bone metastasis is the complex interplay between the cancer cells and the cells of the bone microenvironment, which can occur already before the cancer cells enter the distant site. Cancer cells at the primary site can secrete soluble factors and extracellular vesicles to bone to create a "pre-metastatic niche" i.e., prime the microenvironment permissive for cancer cell homing, survival, and growth. Once in the bone, cancer cells secrete factors to activate the osteoclasts or osteoblasts and the so called "vicious cycle of bone metastases". These pathological cell-cell interactions are largely dependent on secreted proteins. However, increasing evidence demonstrates that secreted RNA molecules, in particular small non-coding microRNAs are critical mediators of the crosstalk between bone and cancer cells. This review article discusses the role of secreted miRNAs in bone metastasis development and progression, and their potential as non-invasive biomarkers.
Topics: Male; Humans; MicroRNAs; Bone Neoplasms; Bone and Bones; Osteoclasts; Osteoblasts; Osteolysis; Tumor Microenvironment
PubMed: 37031329
DOI: 10.1007/s00774-023-01424-z -
Expert Reviews in Molecular Medicine Mar 2023Cancer metastasis is the primary cause of cancer-related deaths. The seeding of primary tumours at a secondary site is a highly inefficient process requiring substantial... (Review)
Review
Cancer metastasis is the primary cause of cancer-related deaths. The seeding of primary tumours at a secondary site is a highly inefficient process requiring substantial alterations in the genetic architecture of cancer cells. These alterations include significant changes in global gene expression patterns. MicroRNAs are small, non-protein coding RNAs which play a central role in regulating gene expression. Here, we focus on microRNA determinants of cancer metastasis and examine microRNA dysregulation in metastatic cancer cells. We dissect the metastatic process in a step-wise manner and summarise the involvement of microRNAs at each step. We also discuss the advantages and limitations of different microRNA-based strategies that have been used to target metastasis in pre-clinical models. Finally, we highlight current clinical trials that use microRNA-based therapies to target advanced or metastatic tumours.
Topics: Humans; MicroRNAs; Neoplasms; RNA, Small Untranslated; Gene Expression Regulation, Neoplastic
PubMed: 36927814
DOI: 10.1017/erm.2023.7 -
Cellular and Molecular Life Sciences :... Sep 2011The human genome contains more than 1,000 microRNA (miRNA) genes, which are transcribed mainly by RNA polymerase II. The canonical pathway of miRNA biogenesis includes... (Review)
Review
The human genome contains more than 1,000 microRNA (miRNA) genes, which are transcribed mainly by RNA polymerase II. The canonical pathway of miRNA biogenesis includes the nuclear processing of primary transcripts (pri-miRNAs) by the ribonuclease Drosha and further cytoplasmic processing of pre-miRNAs by the ribonuclease Dicer. This review discusses the issue of miRNA end heterogeneity generated primarily by Drosha and Dicer cleavage and focuses on the structural aspects of the Dicer step of miRNA biogenesis. We examine the structures of miRNA precursors, both predicted and experimentally determined, as well as the influence of various motifs that disturb the regularity of pre-miRNA structure on Dicer cleavage specificity. We evaluate the structural determinants of the length diversity of miRNA generated by Dicer from different precursors and highlight the importance of asymmetrical motifs. Finally, we discuss the impact of Dicer protein partners on cleavage efficiency and specificity and propose the contribution of pre-miRNA structural plasticity to the dynamics of the dicing complex.
Topics: Humans; MicroRNAs; RNA Precursors; RNA Processing, Post-Transcriptional; Ribonuclease III
PubMed: 21607569
DOI: 10.1007/s00018-011-0726-2