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PubMed2005

DICER-LIKE 4 functions in trans-acting small interfering RNA biogenesis and vegetative phase change in Arabidopsis thaliana.

Arabidopsis thaliana contains four DICER-LIKE (DCL) genes with specialized functions in small RNA biogenesis for RNA interference-related processes. A mutant with defects in DCL4 was identified and analyzed for microRNA- and endogenous, small interfering RNA (siRNA)-related functions. The dcl4-2 mutant contained normal or near-normal levels of microRNAs (21 nt) and heterochromatin-associated siRNAs (24 nt). In contrast, this mutant lacked each of three families of 21-nt trans-acting siRNAs (ta-siRNAs) and possessed elevated levels of ta-siRNA target transcripts. The dcl4-2 mutant resembled an rna-dependent RNA polymerase 6 mutant in that both mutants lacked ta-siRNAs and displayed heterochronic defects in which vegetative phase change was accelerated. Double mutant analyses with dcl2-1, dcl3-1, and dcl4-2 alleles revealed hierarchical redundancy among DCL activities, leading to alternative processing of ta-siRNA precursors in the absence of DCL4. These data support the concept that plants have specialized and compartmentalized DCL functions for biogenesis of distinct small RNA classes.

Arabidopsis↗

PubMed2005

Negative regulation of nuclear divisions in Caenorhabditis elegans by retinoblastoma and RNA interference-related genes.

Short RNA regulatory molecules, microRNAs, and short interfering RNAs participate in a range of developmental gene networks by base-pairing with their target sequences. Consistent with these findings, genes required for the biogenesis and function of short interfering RNAs and microRNAs, dicer (dcr-1 in Caenorhabditis elegans) and argonaute homologs, are essential for development in diverse organisms, including C. elegans. We demonstrate that genes required for the function of short RNAs synergize with the retinoblastoma tumor suppressor homolog lin-35 in negative regulation of the nuclear divisions in the intestine of C. elegans. The level of cyclin E (cye-1) expression is critical for nuclear divisions in the intestine and is elevated in double mutants in lin-35 and RNA interference pathway genes. We propose that RNA interference-related pathways cooperate with retinoblastoma in transcriptional repression of endogenous genes, an example being cyclin E.

Animals↗

PubMed2006

Comprehensive identification of Drosophila dorsal-ventral patterning genes using a whole-genome tiling array.

Dorsal-ventral (DV) patterning of the Drosophila embryo is initiated by Dorsal, a sequence-specific transcription factor distributed in a broad nuclear gradient in the precellular embryo. Previous studies have identified as many as 70 protein-coding genes and one microRNA (miRNA) gene that are directly or indirectly regulated by this gradient. A gene regulation network, or circuit diagram, including the functional interconnections among 40 Dorsal target genes and 20 associated tissue-specific enhancers, has been determined for the initial stages of gastrulation. Here, we attempt to extend this analysis by identifying additional DV patterning genes using a recently developed whole-genome tiling array. This analysis led to the identification of another 30 protein-coding genes, including the Drosophila homolog of Idax, an inhibitor of Wnt signaling. In addition, remote 5' exons were identified for at least 10 of the approximately 100 protein-coding genes that were missed in earlier annotations. As many as nine intergenic uncharacterized transcription units were identified, including two that contain known microRNAs, miR-1 and -9a. We discuss the potential functions of these recently identified genes and suggest that intronic enhancers are a common feature of the DV gene network.

Animals↗

PubMed2005

Aberrant T cell differentiation in the absence of Dicer.

Dicer is an RNaseIII-like enzyme that is required for generating short interfering RNAs and microRNAs. The latter have been implicated in regulating cell fate determination in invertebrates and vertebrates. To test the requirement for Dicer in cell-lineage decisions in a mammalian organism, we have generated a conditional allele of dicer-1 (dcr-1) in the mouse. Specific deletion of dcr-1 in the T cell lineage resulted in impaired T cell development and aberrant T helper cell differentiation and cytokine production. A severe block in peripheral CD8(+) T cell development was observed upon dcr-1 deletion in the thymus. However, Dicer-deficient CD4(+) T cells, although reduced in numbers, were viable and could be analyzed further. These cells were defective in microRNA processing, and upon stimulation they proliferated poorly and underwent increased apoptosis. Independent of their proliferation defect, Dicer-deficient helper T cells preferentially expressed interferon-gamma, the hallmark effector cytokine of the Th1 lineage.

Animals↗

PubMed2006

A comprehensive analysis of common copy-number variations in the human genome.

Segmental copy-number variations (CNVs) in the human genome are associated with developmental disorders and susceptibility to diseases. More importantly, CNVs may represent a major genetic component of our phenotypic diversity. In this study, using a whole-genome array comparative genomic hybridization assay, we identified 3,654 autosomal segmental CNVs, 800 of which appeared at a frequency of at least 3%. Of these frequent CNVs, 77% are novel. In the 95 individuals analyzed, the two most diverse genomes differed by at least 9 Mb in size or varied by at least 266 loci in content. Approximately 68% of the 800 polymorphic regions overlap with genes, which may reflect human diversity in senses (smell, hearing, taste, and sight), rhesus phenotype, metabolism, and disease susceptibility. Intriguingly, 14 polymorphic regions harbor 21 of the known human microRNAs, raising the possibility of the contribution of microRNAs to phenotypic diversity in humans. This in-depth survey of CNVs across the human genome provides a valuable baseline for studies involving human genetics.

Chromosome Mapping↗

PubMed2003

Short hairpin type of dsRNAs that are controlled by tRNA(Val) promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells.

The post-transcriptional gene silencing in animals and plants is called RNA interference (RNAi). Guides for the sequence-specific degradation of mRNA are 21-nt small interfering RNAs (siRNAs) that are generated by Dicer-dependent cleavage from longer double-stranded RNAs (dsRNAs). To examine the relationship between the localization of dsRNA and the target cleavage of RNAi in human cells, we constructed five kinds of dsRNA expression vector that were controlled by tRNA(Val) or U6 promoter. Transcripts of tRNA-dsRNA were consistently localized in the cytoplasm and were efficiently processed by Dicer. In contrast, transcripts of tRNA-dsRNA were not processed in cells that expressed Dicer-directed ribozymes. In addition, transcripts of U6-dsRNA were basically localized in the nucleus and were not significantly processed, unless the transcripts of U6-dsRNAs possessed a microRNA-based loop motif: in the latter case, U6-dsRNAs with a microRNA-based loop were transported to the cytoplasm and were effectively processed. More over, tRNA-dsRNA directed against a mutant k-ras transcript cleaved its target mRNA efficiently in assays of RNAi not only in vitro with a cytoplasmic extract but also in vivo. Therefore, it appears that RNAi in human cells occur in the cytoplasm. Importantly, the same tRNA-dsRNA did not affect the degradation of the normal k-ras mRNA in vitro and in vivo. Our tRNA-dsRNA technology should be a powerful tool for studies of the mechanism of RNAi and the functions of various genes in mammalian cells with potential utility as a therapeutic agent.

Cell Division↗

PubMed2003

Maelstrom, a Drosophila spindle-class gene, encodes a protein that colocalizes with Vasa and RDE1/AGO1 homolog, Aubergine, in nuage.

A hallmark of germline cells across the animal kingdom is the presence of perinuclear, electron-dense granules called nuage. In many species examined, Vasa, a DEAD-box RNA helicase, is found in these morphologically distinct particles. Despite its evolutionary conservation, the function of nuage remains obscure. We have characterized a null allele of maelstrom (mael) and shown that Maelstrom protein is localized to nuage in a Vasa-dependent manner. By phenotypic characterization, we have defined maelstrom as a spindle-class gene that affects Vasa modification. In a nuclear transport assay, we have determined that Maelstrom shuttles between the nucleus and cytoplasm, which may indicate a nuclear origin for nuage components. Interestingly, Maelstrom, but not Vasa, depends on two genes involved in RNAi phenomena, aubergine and spindle-E (spn-E), for its nuage localization. Furthermore, maelstrom mutant ovaries show mislocalization of two proteins involved in the microRNA and/or RNAi pathways, Dicer and Argonaute2, suggesting a potential connection between nuage and the microRNA-pathway.

Active Transport, Cell Nucleus↗

PubMed2005

The contributions of dsRNA structure to Dicer specificity and efficiency.

Dicer processes long double-stranded RNA (dsRNA) and pre-microRNAs to generate the functional intermediates (short interfering RNAs and microRNAs) of the RNA interference pathway. Here we identify features of RNA structure that affect Dicer specificity and efficiency. The data presented show that various attributes of the 3' end structure, including overhang length and sequence composition, play a primary role in determining the position of Dicer cleavage in both dsRNA and unimolecular, short hairpin RNA (shRNA). We also demonstrate that siRNA end structure affects overall silencing functionality. Awareness of these new features of Dicer cleavage specificity as it is related to siRNA functionality provides a more detailed understanding of the RNAi mechanism and can shape the development of hairpins with enhanced functionality.

Base Sequence↗

PubMed2006

Clusters of internally primed transcripts reveal novel long noncoding RNAs.

Non-protein-coding RNAs (ncRNAs) are increasingly being recognized as having important regulatory roles. Although much recent attention has focused on tiny 22- to 25-nucleotide microRNAs, several functional ncRNAs are orders of magnitude larger in size. Examples of such macro ncRNAs include Xist and Air, which in mouse are 18 and 108 kilobases (Kb), respectively. We surveyed the 102,801 FANTOM3 mouse cDNA clones and found that Air and Xist were present not as single, full-length transcripts but as a cluster of multiple, shorter cDNAs, which were unspliced, had little coding potential, and were most likely primed from internal adenine-rich regions within longer parental transcripts. We therefore conducted a genome-wide search for regional clusters of such cDNAs to find novel macro ncRNA candidates. Sixty-six regions were identified, each of which mapped outside known protein-coding loci and which had a mean length of 92 Kb. We detected several known long ncRNAs within these regions, supporting the basic rationale of our approach. In silico analysis showed that many regions had evidence of imprinting and/or antisense transcription. These regions were significantly associated with microRNAs and transcripts from the central nervous system. We selected eight novel regions for experimental validation by northern blot and RT-PCR and found that the majority represent previously unrecognized noncoding transcripts that are at least 10 Kb in size and predominantly localized in the nucleus. Taken together, the data not only identify multiple new ncRNAs but also suggest the existence of many more macro ncRNAs like Xist and Air.

Animals↗

PubMed2025

Identification of circulating miRNA alterations in diabetes patients excluding periodontitis effects: insights into target gene downregulation in diabetic complications.

BACKGROUND: Diabetes mellitus (DM) induces systemic complications through chronic metabolic dysregulation. Circulating exosomal microRNAs (miRNAs) are emerging as key regulators of post-transcriptional gene expression and may drive diabetes-associated pathologies. Although miRNAs have been widely studied in diabetes, the characterization of PD-independent miRNA signatures across tissues remains limited. This study aimed to identify DM-specific miRNA alterations and their contribution to systemic metabolic dysfunction independent of PD. METHODS: Exosomes were isolated from plasma samples, and small RNA sequencing was performed to identify differentially expressed miRNAs (DE-miRs) using the limma R package. Predicted target genes were identified using TargetScan and validated through bulk RNA sequencing datasets from four tissues-foot, kidney, pancreas, and retina. Differentially expressed genes (DEGs) were analyzed, followed by Gene Ontology Biological Process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to elucidate diabetes-related mechanisms. RESULTS: We identified 9 upregulated and 6 downregulated DE-miRs specific to the diabetic group. TargetScan predicted 216 upregulated and 64 downregulated target genes. Functional validation revealed that these genes were enriched in pathways related to glucose metabolism, cellular stress response, and tissue repair. Notably, SREK1 and GLIPR1 were commonly detected across all four tissues, suggesting potential systemic regulators of diabetes-related complications. CONCLUSION: This study suggests that circulating exosomal miRNAs, independent of periodontitis, may function as systemic regulators in diabetes. Unlike previous studies, which did not distinguish co-morbid periodontitis, we specifically defined PD-independent miRNA signatures and validated their cross-organ regulatory effects on target genes. Our results revealed a cross-organ miRNA-mRNA regulatory network and identified common regulatory targets. These findings provide insights into both systemic and organ-specific mechanisms underlying diabetic complications and highlight the potential of miRNAs as biomarkers and therapeutic targets.

Humans↗

PubMed2026

miRNA Target Prediction: An Overview of the Past and Current Tools.

MicroRNAs (miRNAs) are among the most studied molecules in recent years, and since their discovery, many miRNAs have been identified across various species. As members of the non-coding RNA family, miRNAs are key players in post-transcriptional gene regulation. These molecules can inhibit translation or promote degradation of messenger RNA (mRNA) by binding to the 3' untranslated region (UTR) of mRNA, thereby influencing almost all biological processes. To identify a miRNA's biological role, it is essential to predict the target sites to which it binds, a goal made possible through bioinformatics tools. This chapter discusses the bioinformatics tools commonly used for this purpose. Also, it analyzes the main factors considered in target prediction, such as seed match, free energy, conservation, site accessibility, multiple binding site contribution, and machine learning and deep learning approaches. Understanding the principles underlying these predictive methodologies is crucial for advancing one's biological research on miRNAs.

MicroRNAs↗

PubMed2026

Non-coding RNAs and Mitochondrial Dysfunction in Alzheimer's Disease: A Systematic Review.

Alzheimer's disease (AD) is responsible for 70% of dementia cases worldwide, with tau hyperphosphorylation and amyloid-β plaque accumulation representing its core pathological hallmarks. Genetic predisposition, oxidative stress, and neuroinflammation contribute to disease onset and progression. Non-coding ribonucleic acids (ncRNAs) are a class of RNAs which control gene expression and whose dysregulation in AD patients has been linked to amyloid production, neuroinflammation, and mitochondrial dysfunction, which ranges from impaired energy metabolism to disrupted mitochondrial biogenesis and dynamics. Our descriptive systematic review surveyed the involvement of ncRNAs in mitochondrial dysfunction in AD across experimental and clinical literature. We identified multiple microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) that directly regulate mitophagy, mitochondrial biogenesis, mitochondrial autophagic, and apoptotic pathways, mitochondrial dynamics, and protein import mechanisms in AD models. Among the most important candidates demonstrating clinical dysregulation, miR-140 and lncRNA NEAT1 regulate mitophagy, while miR-9, miR-34a, miR-146a, miR-155, and miR-485 are implicated in mitochondrial biogenesis and miR-204 in mitochondrial autophagy. LncRNA BDNF-AS, miR-148a-3p, miR-21-5p, and miR-103a-3p emerged as regulators of the mitochondrial apoptosis pathway with confirmed clinical dysregulation. Multiple ncRNAs control mitochondrial dynamics, of which miR-195, miR-124, and miR-455-3p have also been studied in AD patients. Additionally, several ncRNAs were found to indirectly regulate mitochondrial fission, autophagy, and apoptosis, although the underlying mechanisms require further characterization. Thus, while ncRNA-centered AD research is in its early stages, current mechanistic and translational evidence supports mitochondrially relevant ncRNAs as promising candidates for biomarker and therapeutic development.

Alzheimer Disease↗

PubMed2026

Development and validation of a plasma miRNA-CEA biomarker panel for early detection of lung cancer.

Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the critical need for early detection to improve patient outcomes. This study aimed to develop and validate a plasma microRNA biomarker panel for the early detection of non-small cell lung cancer in a Japanese cohort. We enrolled 525 participants, comprising 261 LC cases and 264 non-LC controls, divided into optimization and validation cohorts. A 12-miRNA panel was optimized and further combined with CEA to enhance diagnostic performance. The miRNA-alone model demonstrated robust performance in both the optimization (AUC = 77.0%) and validation cohorts (AUC = 77.9%). Integration with CEA significantly improved accuracy, achieving AUCs of 86.2% in optimization and 84.9% in validation, with particularly high performance in late-stage cancers (AUC = 94.4%) and squamous cell carcinoma (AUC = 90.7%). Sensitivity and specificity thresholds were evaluated, enabling model customization for diverse clinical scenarios. These findings highlight the potential of the miRNA-CEA panel as a minimally invasive tool for early LC detection, especially in non-smoking populations.

Humans↗

PubMed2026

Design, expression, purification, and application of novel recombinant miR-491 molecules to define the biogenesis and function of miR-491-3p versus -5p in posttranscriptional regulation of UDP-glucuronosyltransferase 1A1.

Interindividual variations in drug metabolism involve various factors, including posttranscriptional gene regulation mechanisms controlled by microRNAs (miRNAs or miRs) derived from the genome. The aim of this study was to use RNA bioengineering technology to produce novel recombinant human miR-491-5p, miR-491-3p, and pre-miR-491 molecules, namely BioRNA/miR-491-5p, BioRNA/miR-491-3p, and BioRNA/pre-miR-491, respectively, and define their functional difference in regulating UDP-glucuronosyltransferase 1A1 (UGT1A1) expression and drug-metabolizing capacity. All 6 BioRNAs were heterologously overexpressed in Escherichia coli (>30% of total RNA) and isolated by fast protein liquid chromatography to high purity (>97%). As BioRNA/pre-miR-491 agents were processed to both 5p and 3p strands in Hep3B and HepG2 cells, BioRNA/miR-491-5p and -3p were selectively processed to 5p and 3p, respectively, and each accumulated to greater levels. Immunoblotting and immunofluorescence studies demonstrated the efficacy of BioRNA/miR-491-3p to suppress UGT1A1 protein levels in Hep3B and HepG2 cells, localized on the endoplasmic reticulum, exhibiting monomeric (∼55 kDa) and oligomeric (∼150 kDa) bands under different conditions, whereas BioRNA/pre-miR-491 and miR-491-5p had no effects. Using a fluorescent substrate, N-butyl-4-(4-hydroxyphenyl)-1,8-naphthalimide, lower UGT1A1 drug-metabolizing capacities were found in cells treated with BioRNA/miR-491-3p. In addition, liquid chromatography-tandem mass spectrometry analysis revealed a 45% reduction of estradiol 3-glucuronidation activity by BioRNA/miR-491-3p in Hep3B cells, whereas formation of estradiol 17-glucuronidation mediated by other UGTs was unchanged. Together, these results underline the role of miR-491-3p in regulating UGT1A1 and its impact on cellular drug-metabolizing capacity while demonstrating the applications of recombinant miRNA agents to delineating the importance of posttranscriptional gene regulation in drug metabolism. SIGNIFICANT STATEMENT: Research on posttranscriptional gene regulation mainly uses miRNA mimics chemically synthesized in vitro. This study successfully produced 6 novel recombinant miR-491 molecules through in vivo fermentation with transfer RNA scaffold and transfer RNA-fused pre-miRNA carrier-based technologies, which were further utilized to delineate the biogenesis and function of miR-491-3p versus -5p in modulating UDP-glucuronosyltransferase 1A1 protein levels and drug-metabolizing capacity. The findings demonstrate the role of miR-491-3p in regulating UDP-glucuronosyltransferase 1A1 and value of recombinant miRNA agents for studying drug metabolism.

Humans↗

PubMed2026

Neuropsychiatric disease mechanisms and interventions from 22q11.2 deletion syndrome experimental studies.

A high genetic predisposition for neuropsychiatric disorders, such as schizophrenia and autism spectrum disorders (ASDs), is 22q11.2 deletion syndrome (22q11DS), caused by a hemizygous microdeletion in the q-arm of human chromosome 22. The deletion most often spans a 3 Mb region, with variable breakpoints ranging from 1.5 to 3 Mb. Experimental studies on 22q11DS have revealed several aspects of the pathophysiology of neuropsychiatric disorders and also identified various interventional and rescue strategies. Herein, we review these strategies by grouping the studies into three main mechanistic categories: (i) microRNA (miR)-mediated, (ii) mitochondrial, and (iii) neural circuit deficits in polygenic deletion, and also briefly describe a few other monogenic mechanisms implicated. Haploinsufficiency of Dgcr8, a 22q11DS gene involved in miR processing, forms the center of miR-mediated mechanisms and rescuing consequent pathophysiology rely on age-dependent, brain region-specific or global replenishment of miRs or their targets. Seven genes in the 22q11.2 genomic region encode mitochondrial proteins and approaches to mitigate these gene deficiencies concentrate on the respective mitochondrial functions affected. We briefly describe other potential monogenic mechanisms for intervention including transcriptional regulation, synaptic release, catecholamine metabolism, and cell-cell adhesion, represented by Tbx1, Sept5, Comt, Arvcf, and Cldn5. We also give examples of how the multifaceted pathophysiological mechanisms and rescue strategies can have convergent effects at the molecular, synaptic, cellular and circuit levels. Based on the experimental interventions identified in the 22q11DS studies, we inform on the supportive therapies possible now and the future potential of curative interventions.

Humans↗

PubMed2026

Expression profiles of miRNAs in ruminant intermediate hosts with cystic echinococcosis.

Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus sensu lato (s.l.), is a parasitic zoonotic disease recognized by the World Health Organization as a neglected tropical disease of significant public health concern. Despite ongoing control programs, CE remains endemic, underlining the need for integrated control strategies that involve new diagnostic and therapeutic tools. Recent investigations have spotlighted microRNAs (miRNAs) as key regulators in parasite development, immunomodulation, and as potential diagnostic and therapeutic targets. In the present research, a molecular study was conducted to investigate hydatid cyst samples (protoscoleces and germinal membranes) collected in southern Italy from different ruminant species (sheep, cattle, and water buffaloes), naturally infected with CE, with the ultimate goal of establishing a more comprehensive picture of miRNA expression patterns in these intermediate hosts. The bioinformatic analysis of hydatid cyst samples revealed 168 mature miRNAs. Among these, egr-miR-10-5p, egr-let-7-5p, and egr-miR-71-5p were the most abundant, with egr-miR-10-5p showing particularly high expression levels. No significant differences in miRNA abundance between host species were found. In contrast, when focusing on the comparison between protoscoleces and sterile germinal membranes, 24 miRNAs were found to be differentially expressed. Targeted qPCR of four selected miRNAs (egr-miR-71-5p, egr-let-7-5p, egr-miR-125-5p, and egr-miR-10-5p) showed clear overexpression in protoscoleces and in fertile germinal membranes compared with sterile ones. The differential miRNA expression patterns provide insight into the molecular mechanisms controlling the parasite's lifecycle and may guide the development of novel intervention methods to enhance CE control in endemic areas.

Animals↗

PubMed2026

Invertebrate miRNA pva-small RNA-11881/pva-miR-11881 as a potential RNA-based therapeutic against white spot syndrome virus in infected shrimp.

Small RNAs and microRNAs (miRNAs) play diverse roles in host virus interactions and hold promise for therapeutic applications. An uncharacterized shrimp miRNA with potent activity against white spot syndrome virus (WSSV), a major double-stranded DNA pathogen in aquaculture, was identified and characterized. Among the 1,239 differentially expressed unannotated small RNAs in Penaeus vannamei hemocytes, one of the most strongly downregulated candidates, termed pva-small RNA-11881 or pva-miR-11881, was predicted to target multiple WSSV genes. A pva-small RNA-11881/pva-miR-11881 isomir that originates from the 5' untranslated region of a host lipase 3-like gene was identified. Its primary transcript contains Drosha and Dicer processing sites, and the precursor exhibits canonical pre-miRNA features. In vivo administration of its primary transcript, pva-pri-miR-11881, significantly reduced WSSV copy number and improved shrimp survival. Mechanistically, pva-miR-11881 directly suppresses crucial WSSV genes WSSV004, WSSV164, and WSSV419 and modulates the host immune response against WSSV infection by enhancing phenoloxidase activity, thereby reducing apoptosis and necrosis, and promoting caspase-1-mediated cell death. These findings reveal that the pva-miR-11881 in P. vannamei holds strong potential as a biotherapeutic agent for managing viral diseases in shrimp.

Animals↗

PubMed2025

Abnormal levels of miRNA in pancreatic cancer are linked to tumor progression by regulating the translation of tumor-associated mRNA.

BACKGROUND: Pancreatic cancer remains one of the most malignant tumors, characterized by limited treatment efficacy. MAIN FINDINGS: microRNAs (miRNAs) play a crucial role in regulating the proliferation, invasion, migration, drug resistance, apoptosis, and cell cycle progression of pancreatic cancer cells by inhibiting tumor-associated proteins. Metscape analysis revealed that miRNA-targeted proteins associated with pancreatic cancer are enriched in processes such as cell proliferation, mitosis, and cell migration, and participate in multiple signaling pathways. These proteins primarily localize to classical pathways, including JAK/STAT, PI3K/AKT, and Wnt/β-catenin. Furthermore, gene mutations or abnormal alternative poly(A)denylation (APA) within miRNA-targeted regions can disrupt base pairing to the 3'-Untranslated Region (3'-UTR), thereby enhancing the translation of oncogenic mRNA translation. FUTURE DIRECTIONS: Collectively, these findings indicate that multiple miRNAs act cooperatively to influence pancreatic cancer progression. Consequently, therapeutic strategies aimed at restoring the balance of the miRNA system are essential to disrupt the 'mRNA-oncogene' vicious cycle.

Humans↗