MicroRNA - Volume 14, Issue 2, 2025
Volume 14, Issue 2, 2025
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Extrahepatic and Circulating miR-122: Diagnostic Implications and Future Directions
More LessAuthors: Rachel Sarah Royfman, Joseph Riley McTague, Meghana Ranabothu and Bindu MenonResearch on microRNAs is constantly expanding and evolving due to their role in the regulation of gene expression. miR-122, a 22-nucleotide microRNA, was first discovered as a liver-specific miRNA. Subsequently, it was found to be present in a wide range of tissues, such as the breast, testes, ovaries, and heart. The research on miR-122 in the liver has been extensive over the past few decades, leading to several important discoveries. However, its role in extrahepatic tissues is largely incompletely understood. Therefore, in light of the established clinical relevance of miR-122 as a potential biomarker and/or drug target in the liver, available information on miR-122 is compiled as it pertains to health and disease. This review discusses novel information generated in recent years and the corresponding progress in our understanding of the physiology of extrahepatic miR-122.
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Nanoparticle Carriers: A New Era of Precise CRISPR/Cas9 Gene Editing
More LessAuthors: Bhawna Sharma, Iti Chauhan, Gaurav Kumar, Khushboo Bhardwaj and Raj Kumar TiwariThe revolutionary CRISPR/Cas9 gene editing technology holds immense potential for treating genetic diseases and tackling conditions like cancer. However, efficient delivery remains a significant challenge. This is where nanoparticles come into play, emerging as powerful allies in the realm of drug delivery. Nanoparticles can accommodate larger insertion sizes, enabling the incorporation of larger Cas9 enzymes and complex guide RNAs, thus opening up the possibility of editing previously inaccessible genetic regions. Their relatively straightforward and scalable production processes make them cost-effective options for wider applications. Notably, nanoparticles excel in vivo, demonstrating efficient tissue penetration and targeted delivery, which are crucial for maximizing therapeutic impact while minimizing side effects.
This review aims to explore the potential of nanoparticle-based delivery systems for CRISPR/Cas9, highlighting their advantages and challenges in gene editing applications. The diverse range of nanoparticles further bolsters their potential. Polymeric nanoparticles, for instance, offer tunable properties for customization and controlled release of the CRISPR cargo. Lipid-based nanoparticles facilitate efficient cellular uptake and endosomal escape, ensuring the CRISPR components reach the target DNA. Even gold nanoparticles, known for their unique biocompatibility and photothermal properties, hold promise in light-activated editing strategies. Non-viral delivery systems, particularly those based on nanoparticles, stand out due to their inherent advantages.
Collectively, the evidence paints a promising picture: nanoparticles are not merely passive carriers but active participants in the CRISPR/Cas9 delivery landscape. Their versatility, efficiency, and safety position them as key enablers of a future where gene editing can revolutionize drug development, offering personalized and targeted therapies for a wide range of diseases.
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A Robust NSCLC Biomarker- miR-7-5p: Its In-Silico Validation and Potential SPR-Based Probe for Detection
More LessAuthors: Chandrajeet Dhara, Anindita Dhara and Saumyatika GantayatMicroRNA abundance as a particular biomarker for precisely identifying cancer metastases has emerged in recent years. The expression levels of miRNA are analyzed to get insights into cancer tissue detection and subtypes. Similar to other cancer types, the miRNA shows high levels of target mRNA dysregulation in association with non-small cell lung carcinoma (NSCLC). Among many promising cancer biomarkers for NSCLC, miR-7-5p has shown significant downregulation in the NSCLC tissues and targets proto-oncogenes like PAK2 and NOVA2. The expression levels of different proto-oncogenes targeting the miR-7-5p in NSCLC showed that the EGFR-mutated NSCLC has an experimental validation. The target validation of the miR-7-5p could be analyzed using SPR (Surface plasmon resonance) based sensors at a single nanoparticle level, such as Au nanocube, due to its high specificity and accountability. Despite being an accountable tool for cancer diagnosis, miRNA-based biomarkers sometimes cause poor diagnostic specificity and reproducibility due to their heterogenicity and immunogenicity in cancer detection. To overcome these shortcomings, the biomarkers need to be validated according to recent clinical studies.
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Key LncRNAs Associated with Distant Metastasis in Breast Cancer: A System Biology Analysis
More LessIntroductionBreast cancer (BC) is the most prevalent cancer among women globally. Metastasis is the leading cause of mortality in most cancers. Early BC detection before metastasis can enhance survival rates. Understanding BC metastasis mechanisms could aid in developing metastasis-specific treatments.
MethodsThe role of long non-coding RNAs (lncRNA) in cancer progression is recognized, yet the importance of specific lncRNAs in BC, despite potential alterations, remains inadequately explored. We utilized bioinformatics tools to identify novel lncRNAs dysregulated in metastasis. To achieve this objective, the gene expression profile of GSE102484, encompassing metastatic and non-metastatic BC tissue samples, was analyzed using the limma package in R with cut-off criteria set at an adjusted p-value < 0.005 and |fold change (FC)| ≥ 0.5. We used WGCNA analysis to find co-expression genes for lncRNAs. Then, we identified hub genes and performed pathway enrichment to better understand the results. Considering the defined criteria, eight novels of dysregulated lncRNAs and top 10 miRNAs were identified.
ResultsDysregulated lncRNAs are found in yellow, green, brown, purple, and turquoise co-expression modules from WGCNA analysis. Enrichment analysis of these co-expressed modules revealed relevant pathways to metastasis, such as epithelial-to-mesenchymal transition and integrin cell-surface interactions, as well as regulation of HIF1-alpha. In addition, SDPR, TGFB1I1, ILF3, KIF4A, and COL5A1 were identified as hub genes. Based on DElncRNA-miRNA-DEmRNA connections and co-expression, we ultimately constructed lncRNA-associated ceRNA axes.
ConclusionThe current study may identify novel lncRNAs implicated in BC metastasis; still, additional research is required to determine the potential functions of these lncRNAs in BC metastasis.
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Evaluation of Salivary and Serum micro RNA 146a, 200c and its Target Gene PTEN in Chronic Periodontitis Patients and their Response to Non-Surgical Periodontal Therapy
More LessAuthors: Jammula Surya Prasanna and Kunnel ApoorvaBackgroundPeriodontitis destroys the tooth's supporting structures and attachment apparatus. Local or systemic factors can cause it. Traditionally, diagnosis is based on clinical parameters that may not consistently reflect an accurate confirmation. Biochemical and genetic analyses can provide deeper insights. MicroRNAs (miRNAs) regulate the immune and inflammatory response to microbial pathogens. Detecting and evaluating miRNAs can be an important diagnostic parameter. This study aimed to assess the expression of miRNA 146a,200c, and its target gene PTEN to non-surgical periodontal therapy in serum and saliva.
Materials and MethodsThis interventional comparative study was conducted on 120 patients of both genders, ages between 35 and 55. Non-surgical periodontal therapy (NSPT) scaling and root planing were performed on all subjects, and their saliva and serum samples were collected before and after 8 weeks of NSPT. Quantitative rt-PCR (reverse transcriptase Polymerase Chain Reaction) analysis was conducted on all samples. The statistical analysis was done using SPSS version 22, and comparisons were made using paired t-tests, independent t-tests, and Pearson’s correlation coefficient. The statistical significance level was set at a ‘P’ value of less than 0.05.
ResultsIt has been observed that there was a significant difference of miRNA in both serum and saliva samples 146a,200c, and the PTEN gene expression, from the beginning to 8 weeks. Significant variation was not observed when comparing the levels between serum and saliva.
ConclusionmiRNA 146A, 200c, and PTEN genes are interrelated with periodontitis. We can consider them as future biomarkers of periodontal diseases.
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A Potential Regulatory Network of Selected Human Erythrocytic miRNAs with Plasmodium falciparum 3D7 mRNAs: A Computational Analysis
More LessAuthors: Urja Joshi, Harsha Motwani, Dhara Jani, Linz-buoy George and Hyacinth HighlandBackgroundmiRNAs are small non-coding conserved RNA molecules (18-24 nts) that act as crucial gene regulators via post-transcriptional/translational modifications through interacting with the respective mRNAs during various pathophysiological conditions. Recent research has suggested that non-coding RNAs, particularly miRNAs, can be passed from one species to another to regulate gene expression. Since miRNA-mediated gene regulation has not yet been found in Plasmodia, it is hypothesized that erythrocytic miRNAs from Plasmodium falciparum (P. falciparum) could potentially migrate from the cytoplasm to the parasitophorous vacuole developed intracellularly by the parasite to regulate its transcriptome.
ObjectiveThe objective of this study is to investigate the role of trans-kingdom interactions in host-parasite dynamics and their implications for malaria infection.
MethodsUsing the trans-kingdom target gene prediction tool, psRNA target server, a total of 15 human erythrocytic miRNAs from 12 distinct families were selected and obtained from miRBase to find potential P. falciparum candidate genes. This study utilized ShinyGO (version 0.80) for gene enrichment analysis with statistical analysis of the selected features. The PPI-network analysis was performed using the Maximal Clique Centrality (MCC) approach, along with the CytoHubba plugin for identifying hub nodes. The PPI network was visualized using Cytoscape version 3.7.
ResultsA total of 145 target genes of Pf3D7 were predicted, with the following genes repeatedly targeted: conserved Plasmodium proteins, conserved Plasmodium membrane proteins, PfEMP1, rifin, RAD54, E3 ubiquitin-protein ligase, and transcription factors related genes. Outputs of ShinyGO included enriched GO pathways of 62 uniquely identified Pf3D7 genes with detailed descriptions and visualized networks. For overlapping relationships, a hierarchical clustering tree of enriched gene sets was carried out, along with a genome plot for representing the chromosomal locations of these genes. According to their coding-noncoding distribution chart, most of these genes were found to be members of the coding gene family. Additionally, PPI-network analysis reported the top 10 hub nodes: PFE0400w, MAL13P1.380, MAL7P1.167, PFD0900w, PF11_0243, PFE0440w, PFE1120w, MAL13P1.315, PF08_0126, and MAL8P1.23. Three KEGG pathway diagrams of pfa 05144 for Malaria, pfa 03440 for homologous recombination, and pfa 00750 for vitamin B6 metabolism with identified Pf3D7 genes were drawn and highlighted in red.
ConclusionThe important target genes of Plasmodium falciparum 3D7 were identified by carrying out a trans-kingdom investigation, thus offering preliminary insights into the potential of erythrocytic miRNAs-mediated trans-kingdom regulation.
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Identification of Key miRNAs in Endometriosis
More LessIntroductionEndometriosis, a prevalent gynecological disorder characterized by the presence of endometrial-like tissue outside the uterus, poses significant challenges in diagnosis and management due to its unclear pathogenesis and lack of specific biomarkers.
ObjectiveThis study investigates the potential use of microRNAs (miRNAs) as key markers in endometriosis by studying two cohorts of patients (14 patients diagnosed with endometriosis and 15 patients with gynecological benign lesions, different from endometriosis).
MethodsMicroRNA sequencing analysis was tested within data management by a custom pipeline designed by Eurofins Genoma Group.
ResultsWe identified a specific miRNA expression profile associated with endometriosis to feature specific disease molecular clusters to further elucidate the underlying mechanisms driving endometriosis pathogenesis.
Data from the present study suggest a specific miRNA scar for endometriosis compared to other gynecological diseases to develop screening tools in early diagnosis and to ameliorate the management of the disease itself.
ConclusionThis study lays the foundation for the identification of key miRNAs involved in the disease pathogenesis to unveil the molecular signatures in the complex scenario of endometriosis. Further validation and exploration of these findings are needed to develop tools to improve molecular diagnosis and to create a machine-learning prediction algorithm in the future.
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