microRNA Pathway Research Articles

Blood-Based Biomarkers in Alzheimer's Disease: Advancing Non-Invasive Diagnostics and Prognostics.

Alzheimer's disease (AD), the most prevalent form of dementia, is expected to rise dramatically in incidence due to the global population aging. Traditional diagnostic approaches, such as cerebrospinal fluid analysis and positron emission tomography, are expensive and invasive, limiting their routine clinical use. Recent advances in blood-based biomarkers, including amyloid-beta, phosphorylated tau, and neurofilament light, offer promising non-invasive alternatives for early AD detection and disease monitoring. This review synthesizes current research on these blood-based biomarkers, highlighting their potential to track AD pathology and enhance diagnostic accuracy. Furthermore, this review uniquely integrates recent findings on protein-protein interaction networks and microRNA pathways, exploring novel combinations of proteomic, genomic, and epigenomic biomarkers that provide new insights into AD's molecular mechanisms. Additionally, we discuss the integration of these biomarkers with advanced neuroimaging techniques, emphasizing their potential to revolutionize AD diagnostics. Although large-scale validation is still needed, these biomarkers represent a critical advancement toward more accessible, cost-effective, and early diagnostic tools for AD.

FMRP cooperates with miRISC components to repress translation and regulate neurite morphogenesis in Drosophila

ABSTRACT Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability and is caused by mutations in the gene encoding the Fragile X messenger ribonucleoprotein (FMRP). FMRP is an evolutionarily conserved and neuronally enriched RNA-binding protein (RBP) with functions in RNA editing, RNA transport, and protein translation. Specific target RNAs play critical roles in neurodevelopment, including the regulation of neurite morphogenesis, synaptic plasticity, and cognitive function. The different biological functions of FMRP are modulated by its cooperative interaction with distinct sets of neuronal RNA and protein-binding partners. Here, we focus on interactions between FMRP and components of the microRNA (miRNA) pathway. Using the Drosophila S2 cell model system, we show that the Drosophila ortholog of FMRP (dFMRP) can repress translation when directly tethered to a reporter mRNA. This repression requires the activity of AGO1, GW182, and MOV10/Armitage, conserved proteins associated with the miRNA-containing RNA-induced silencing complex (miRISC). Additionally, we find that untagged dFMRP can interact with a short stem-loop sequence in the translational reporter, a prerequisite for repression by exogenous miR-958. Finally, we demonstrate that dFmr1 interacts genetically with GW182 to control neurite morphogenesis. These data suggest that dFMRP may recruit the miRISC to nearby miRNA binding sites and repress translation via its cooperative interactions with evolutionarily conserved components of the miRNA pathway.

Circular RNA ACVR2A promotes the progression of hepatocellular carcinoma through mir-511-5p targeting PI3K-Akt signaling pathway

Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway.In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.

P-268 Unique Argonaute isoforms from mammalian oocytes: unveiling their true purpose

Abstract Study question How does the mouse oocyte-specific AGO2 isoform (AGO2ooc) affect RNA interference (RNAi) and microRNA (miRNA) pathways? Summary answer Mouse AGO2ooc presents reduced RNAi-like endonucleolytic cleavage of perfectly complementary targets. Functional analysis of its impact on fertility and oocyte transcriptome control is in progress. What is known already Argonaute proteins play a pivotal role in effector complexes dedicated to miRNA and RNAi pathways, where small RNAs mediate sequence-specific repression of target RNAs. While all mammalian AGO proteins (AGO1 to AGO4) can function in the miRNA pathway, inhibiting target translation, AGO2 uniquely engages in the RNAi pathway, directing the endonucleolytic cleavage of targets perfectly complementary to small RNAs. In mammalian somatic cells, miRNAs are part of a crucial posttranscriptional regulation network, while RNAi is mostly non-functional. Mouse oocytes, however, deviate from this norm: miRNA regulation proves dispensable, while the abrogation of RNAi results in meiotic spindle defects and sterility. Study design, size, duration Experimental study. Participants/materials, setting, methods We pooled 25 fully-grown GV oocytes in triplicates from non-stimulated 10-12 weeks-old C57BI/6NCrl females for RNA isolation and sequencing. To assess RNAi-like and miRNA-like activity, we transfected Ago2ooc/ooc clones and WT cells with NanoLuc luciferase reporters bearing one perfect complementary (1xP, RNAi-like), four bulged (4xB, miRNA-like) or four mutated (4xM, control) sites for Let-7a and miR-30c. A firefly luciferase reporter without any site was co-transfected for normalization purposes. Main results and the role of chance RNA sequencing revealed an alternative exon-1 in mouse oocyte AGO2, producing an isoform (AGO2ooc) with different amino acid composition in the N-terminus. Interestingly, the somatic version of this N-terminus presents amino acid residues known to be post-translationally modified. These residues are absent in AGO2ooc. To functionally analyze the oocyte-specific N-terminus, we genetically engineered NIH3T3 fibroblasts to express the oocyte alternative exon-1 (Ago2ooc/ooc). Notably, AGO2ooc-expressing cells presented reduced RNAi-like (2-5 fold) but indistinguishable miRNA-like activity when compared to WT cells in reporter assays for Let-7a and miR-30c. The lower RNAi-like activity presented by AGO2ooc-expressing cells was further confirmed in an independent RNAi assay employing the expression of dsRNA hairpins. Both isoforms showed similar abundance in fibroblasts and similar cleavage activity in vitro. Next, we wondered whether AGO2ooc also displays reduced RNAi activity in vivo. To answer that, we generated mouse models whose oocytes would express the somatic AGO2 isoform instead of the AGO2ooc, or N-terminal variants with mutations in putative key amino acid residues. These models will be further utilized to assess fertility and oocyte transcriptome. Limitations, reasons for caution We must investigate whether AGO2ooc also displays differential RNAi activity in mouse oocytes and is relevant for oocyte competence, using the developed mouse models. Wider implications of the findings Mouse oocytes are known to exceptionally operate RNAi. Remarkably, AGO2, the effector nuclease associated with RNAi-like target cleavage has a different N-terminus in oocytes, suggesting that this factor could have adapted to this atypical regulation. We hypothesize that AGO2ooc controls RNAi repression, gene expression and oocyte competence. Trial registration number not applicable

Micromanaging the neuroendocrine system - A review on miR-7 and the other physiologically relevant miRNAs in the hypothalamic-pituitary axis.

The hypothalamic-pituitary axis is central to the functioning of the neuroendocrine system and essential for regulating physiological and behavioral homeostasis and coordinating fundamental body functions. The expanding line of evidence shows the indispensable role of the microRNA pathway in regulating the gene expression profile in the developing and adult hypothalamus and pituitary gland. Experiments provoking a depletion of miRNA maturation in the context of the hypothalamic-pituitary axis brought into focus a prominent involvement of miRNAs in neuroendocrine functions. There are also a few individual miRNAs and miRNA families that have been studied in depth revealing their crucial role in mediating the regulation of fundamental processes such as temporal precision of puberty timing, hormone production, fertility and reproduction capacity, and energy balance. Among these miRNAs, miR-7 was shown to be hypothalamus-enriched and the top one highly expressed in the pituitary gland, where it has a profound impact on gene expression regulation. Here, we review miRNA profiles, knockout phenotypes, and miRNA interaction (targets) in the hypothalamic-pituitary axis that advance our understanding of the roles of miRNAs in mammalian neurosecretion and related physiology.

Disruption of microRNA pathway core genes inhibits molting and reproduction of the cigarette beetle, Lasioderma serricorne.

MicroRNA (miRNA) pathway genes have been widely reported to participate in several physiological events in insect lifecycles. The cigarette beetle Lasioderma serricorne is an economically important storage pest worldwide. However, the functions of miRNA pathway genes in L. serricorne remain to be clarified. Herein, we investigated the function of molting and reproduction of the miRNA pathway in L. serricorne. LsDicer-1, LsArgonaute-1, LsLoquacious and LsExportin-5 were universally expressed in adults, whereas LsPasha and LsDrosha were mainly expressed in the pupae. The genes presented different patterns in various tissues. Silencing of LsDicer-1, LsArgonaute-1, LsDrosha and LsExportin-5 resulted in a high proportion of wing deformities and molting defects. Silencing of LsDicer-1, LsArgonaute-1, LsPasha and LsLoquacious affected the development of the ovary and the maturation of oocytes, resulting in a significant decrease in fecundity. Further investigation revealed that the decreases in LsDicer-1 and LsArgonaute-1 expression destroyed follicular epithelia and delayed vitellogenesis and oocyte development. In addition, the expression levels of several miRNAs (let-7, let-7-5p, miR-8-3p, miR-8-5p, miR-9c-5p, miR-71, miR-252-5p, miR-277-3p, miR-263b and Novel-miR-50) were decreased significantly after knockdown of these miRNA pathway core genes, indicating that they played important roles in regulating miRNA-mediated gene expression. The results indicate that miRNA pathway genes play important roles in the molting, ovarian development and female fecundity of L. serricorne, and thus are potentially suitable target genes for developing an RNAi strategy against a major pest of stored products. © 2024 Society of Chemical Industry.

The Combined Impact of Curcumin: Piperine and Sorafenib on microRNAs and Different Pathways in Breast Cancer Cells

The Combined Impact of Curcumin: Piperine and Sorafenib on microRNAs and Different Pathways in Breast Cancer Cells

Zhilong Huoxue Tongyu Capsule Ameliorates Platelet Aggregation and Thrombus Induced by Aspirin in Rats by Regulating Lipid Metabolism and MicroRNA Pathway.

Zhilong Huoxue Tongyu capsule (ZLHX) is a traditional Chinese medicinal compound preparation, which exhibits obvious therapeutic effects on aspirin resistance (AR). However, the mechanism of ZLHX on AR is rarely reported. This study aimed to explore the therapeutic effects of AR and the underlying mechanisms of ZLHX on AR rats. An AR model was established through treatment with a high-fat, high-sugar, and highsalt diet for 12 weeks and oral administration of aspirin (27 mg/kg/day) and ibuprofen (36 mg/kg/day) in weeks 9-12. The rats were administrated with ZLHX (225, 450, and 900 mg/kg) from week 12 to week 16. Blood samples were collected after the experiment. Thromboelastography analysis was performed, and the levels of triglyceride (TG), total cholesterol (TC), lowdensity lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were determined. Furthermore, the levels of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6- keto-PGF1α) were determined with commercial ELISA kits. Finally, the gene expressions of microRNA- 126-3p (miRNA-126-3p) and miRNA-34b-3p were detected through a real-time quantitative polymerase chain reaction. Results demonstrated that ZLHX significantly inhibited platelet aggregation in the AR rats. Moreover, ZLHX markedly decreased the levels of TC, TG, and LDL-C and increased the level of HDL-C. Meanwhile, ELISA results confirmed that ZLHX can elevate the expression levels of TXB2 and 6-keto-PGF1α. Further studies suggested that ZLHX significantly downregulated the expression levels of miRNA-126-3p and miRNA-34b-3p. This study revealed that the therapeutic effect of ZLHX might be related to the regulation of lipid metabolism and the miRNA pathway.

Identification and expression patterns of somatic piRNAs and PIWI genes in Riptortus pedestris (Hemiptera: Alydidae).

RNA interference (RNAi)-based gene silencing is a feasible and sustainable technology for the management of hemipteran pests by double-stranded RNA involvement, including small-interfering RNA, microRNA, and Piwi-interacting RNA (piRNA) pathways, that may help to decrease the usage of chemical insecticides. However, only a few data are available on the somatic piRNAs and their biogenesis genes in Riptortus pedestris, which serves as a significant pest of soybean (Glycine max). In this study, two family members of the PIWI gene were identified and characterized in R. pedestris, containing Argonaute3 (RpAgo3) and Aubergine (RpAub) genes with conserved protein domains, and their clusters were validated by phylogenetic analysis. In addition, they were widely expressed in all developmental stages of the whole body of R. pedestris and had lower expression levels in R. pedestris guts under different rearing conditions based on previous transcriptome sequencing. Furthermore, abundant clean reads were filtered to a total number of 45,998 piRNAs with uridine bias at the first nucleotide (nt) position and 26-32 nt in length by mapping onto the reference genome of R. pedestris according to our previous whole-transcriptome sequencing. Finally, our data revealed that gut bacterial changes were significantly positively or negatively associated with differentially expressed piRNAs among the five comparison groups with Pearson correlation analysis. In conclusion, these findings paved new avenues for the application of RNAi-based biopesticides for broad-spectrum hemipteran pest control.

Importance of core microRNA pathway genes and microRNAs associated with the defense of Odontotermes formosanus (Shiraki) against Serratia marcescens infection

MicroRNAs (miRNAs) are noncoding small regulatory RNAs involved in diverse biological processes. Odontotermes formosanus (Shiraki) is a polyphagous pest that causes economic damage to agroforestry. Serratia marcescens is a bacterium with great potential for controlling this insect. However, knowledge about the miRNA pathway and the role of miRNAs in O. formosanus defense against SM1 is limited. In this study, OfAgo1, OfDicer1 and OfDrosha were differentially expressed in different castes and tissues. SM1 infection affected the expression of all three genes in O. formosanus. Then, we used specific double-stranded RNAs to silence OfAgo1, OfDicer1 and OfDrosha. Knockdown of these genes enhanced the virulence of SM1 to O. formosanus, suggesting that miRNAs were critical in the defense of O. formosanus against SM1. Furthermore, we sequenced miRNAs from SM1-infected and uninfected O. formosanus. 33 differentially expressed (DE) miRNAs were identified, whereby 22 were upregulated and 11 were downregulated. Finally, the miRNA-mRNA networks were constructed, which further suggested the important role of miRNAs in the defense of O. formosanus against SM1. Totally, O. formosanus miRNA core genes defend against SM1 infection by regulating miRNA expression. This study elucidates the interactions between O. formosanus and SM1 and provides new theories for biological control.

Defining the contribution of microRNA-specific Argonautes with slicer capability in animals.

microRNAs regulate gene expression through interaction with an Argonaute protein. While some members of this protein family retain an enzymatic activity capable of cleaving RNA molecules complementary to Argonaute-bound small RNAs, the role of the slicer residues in the canonical microRNA pathway is still unclear in animals. To address this, we created Caenorhabditis elegans strains with mutated slicer residues in the endogenous ALG-1 and ALG-2, the only two slicing Argonautes essential for the miRNA pathway in this animal model. We observe that the mutation in ALG-1 and ALG-2 catalytic residues affects overall animal fitness and causes phenotypes reminiscent of miRNA defects only when grown and maintained at restrictive temperature. Furthermore, the analysis of global miRNA expression shows that the slicer residues of ALG-1 and ALG-2 contribute differentially to regulate the level of specific subsets of miRNAs in young adults. We also demonstrate that altering the catalytic tetrad of those miRNA-specific Argonautes does not result in any defect in the production of canonical miRNAs. Together, these data support that the slicer residues of miRNA-specific Argonautes contribute to maintaining levels of a set of miRNAs for optimal viability and fitness in animals particularly exposed to specific growing conditions.

The SLC19A1-AS/miR-1343/WNT11 axis is a novel positive regulatory ceRNA network governing goat granulosa cell proliferation

Long noncoding RNAs (lncRNAs), as competitive endogenous RNAs (ceRNAs), can directly or indirectly affect the proliferation and apoptosis of granulosa cells by regulating microRNA (miRNA) pathways. A ceRNA network of the SLC19A1-AS-miR-1343-WNT11 axis was constructed via comprehensive transcriptome sequencing of ovaries from goats with various fertility levels to further elucidate the function and regulatory mechanism of SLC19A1-AS in modulating miR-1343 and WNT11 during granulosa cell proliferation and apoptosis. Subsequent validation experiments were conducted in vitro using granulosa cells. In these experiments, we performed RNA immunoprecipitation (RIP) and identified SLC19A1-AS as a ceRNA in goat granulosa cells that promoted proliferation. Through bioinformatics prediction, luciferase reporter gene assays, and RNA pulldown assays, we confirmed that SLC19A1-AS acts as a sponge for miR-1343, preventing its binding to WNT11 mRNA and thereby increasing the expression of WNT11. This interaction also influenced the proliferation and apoptosis of granulosa cells. Our study systematically validated the biological function of the lncRNA–miRNA-mRNA ceRNA network in goat ovaries and revealed the potential regulatory mechanism by which SLC19A1-AS functions as a ceRNA in granulosa cells. These findings are expected to provide an important experimental foundation for further elucidating the physiological regulatory network of the ovary and contributing to reproductive health in goats.

A Review of Proposed Mechanisms in Rheumatoid Arthritis and Therapeutic Strategies for the Disease.

Rheumatoid arthritis (RA) is characterized by synovial edema, inflammation, bone and cartilage loss, and joint degradation. Patients experience swelling, stiffness, pain, limited joint movement, and decreased mobility as the condition worsens. RA treatment regimens often come with various side effects, including an increased risk of developing cancer and organ failure, potentially leading to mortality. However, researchers have proposed mechanistic hypotheses to explain the underlying causes of synovitis and joint damage in RA patients. This review article focuses on the role of synoviocytes and synoviocytes resembling fibroblasts in the RA synovium. Additionally, it explores the involvement of epigenetic regulatory systems, such as microRNA pathways, silent information regulator 1 (SIRT1), Peroxisome proliferatoractivated receptor-gamma coactivator (PGC1-α), and protein phosphatase 1A (PPM1A)/high mobility group box 1 (HMGB1) regulators. These mechanisms are believed to modulate the function of receptors, cytokines, and growth factors associated with RA. The review article includes data from preclinical and clinical trials that provide insights into potential treatment options for RA.

AGO1 controls protein folding in mouse embryonic stem cell fate decisions

Argonaute (AGO) proteins are evolutionarily conserved RNA-binding proteins that control gene expression through the small RNAs they interact with. Whether AGOs have regulatory roles independent of RNAs, however, is unknown. Here, we show that AGO1 controls cell fate decisions through facilitating protein folding. We found that in mouse embryonic stem cells (mESCs), while AGO2 facilitates differentiation via the microRNA (miRNA) pathway, AGO1 controls stemness independently of its binding to small RNAs. We determined that AGO1 specifically interacts with HOP, a co-chaperone for the HSP70 and HSP90 chaperones, and enhances the folding of a set of HOP client proteins with intrinsically disordered regions. This AGO1-mediated facilitation of protein folding is important for maintaining stemness in mESCs. Our results demonstrate divergent functions between AGO1 and AGO2 in controlling cellular states and identify an RNA-independent function of AGO1 in controlling gene expression and cell fate decisions.

Cav3.1 T-type calcium channel blocker NNC 55-0396 reduces atherosclerosis by increasing cholesterol efflux

Calcium channel blockers (CCBs) are commonly used as antihypertensive agents. While certain L-type CCBs exhibit antiatherogenic effects, the impact of Cav3.1 T-type CCBs on antiatherogenesis and lipid metabolism remains unexplored. NNC 55–0396 (NNC) is a highly selective blocker of T-type calcium channels (Cav3.1 channels). We investigated the effects of NNC on relevant molecules and molecular mechanisms in human THP-1 macrophages. Cholesterol efflux, an indicator of reverse cholesterol transport (RCT) efficiency, was assessed using [3H]-labeled cholesterol. In vivo, high cholesterol diet (HCD)-fed LDL receptor knockout (Ldlr-/-) mice, an atherosclerosis-prone model, underwent histochemical staining to analyze plaque burden. Treatment of THP-1 macrophages with NNC facilitated cholesterol efflux and reduced intracellular cholesterol accumulation. Pharmacological and genetic interventions demonstrated that NNC treatment or Cav3.1 knockdown significantly enhanced the protein expression of scavenger receptor B1 (SR-B1), ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and liver X receptor alpha (LXRα) transcription factor. Mechanistic analysis revealed that NNC activates p38 and c-Jun N-terminal kinase (JNK) phosphorylation, leading to increased expression of ABCA1, ABCG1, and LXRα-without involving the microRNA pathway. LXRα isrequired for NNC–induced ABCA1 and ABCG1 expression. Administering NNC diminished atherosclerotic lesion area and lipid deposition in HCD-fed Ldlr-/- mice. NNC's anti-atherosclerotic effects, achieved through enhanced cholesterol efflux and inhibition of lipid accumulation, suggest a promising therapeutic approach for hypertensive patients with atherosclerosis. This research highlights the potential of Cav3.1 T-type CCBs in addressing cardiovascular complications associated with hypertension.

Serum exosomal microRNA pathway activation in placenta accreta spectrum: pathophysiology and detection

BackgroundPlacenta Accreta Spectrum (PAS) disorders are a complex range of placental pathologies associated with significant maternal morbidity and mortality. Diagnosis of PAS relies on ultrasonographic findings with modest positive predictive value. Exosomal microRNA (miR) are small RNA molecules which reflect the cellular processes of origin tissues. ObjectiveWe aimed to explore exosomal miR expression to understand PAS pathology and clinical utility for PAS detection. Study designThis study was a biomarker analysis of prospectively collected samples in two academic institutions from 2011-2022. Plasma specimens were collected from patients with suspected PAS, placenta previa or repeat cesarean section. Exosomes were quantified and characterized by nanoparticle tracking analysis and Western blot. MiR were assessed by PCR array and targeted single quantification. MiR pathway analysis was performed using Ingenuity® Pathway Analyses software. Placental biopsies were taken from all groups and analyzed by PCR and whole cell ELISA. ROC univariate analysis was performed for microRNA prediction of PAS. Clinically relevant outcomes were collected from abstracted medical records. ResultsPlasma specimens were analyzed from a total of 120 subjects (60 PAS, 30 placenta previa and 30 control). Isolated plasma exosomes had a mean size of 71.5 nm and were ten times greater in PAS specimens (20 vs 2 particles/frame). Protein expression of exosomes were positive for ICAM-1, Flotilin, Annexin and CD9. MiR analysis showed increased detection of three miRs (mir-92/103/192) in patients with PAS. Pathway interaction assessment revealed differential regulation of p53 signaling in PAS and ERBB2/HER2 in control specimens. These findings were subsequently confirmed in placental protein analysis. Placental miR paralleled plasma exosomal miR expression. Biomarker assessment of PAS-signature miR had an AUC=0.81 (p< 0.001, 95% CI [0.73-0.89]) with a sensitivity and specificity of 89.2% and 80%, respectively. ConclusionIn this large cohort, plasma exosomal miR assessment revealed differentially expressed pathways in PAS and are potential biomarkers for the detection of PAS.

Functional characteristics of Dicer genes in Plutella xylostella.

Dicer is an endonuclease that belongs to the RNase III family and can specifically recognize and cleave double-stranded RNA (dsRNA). In most insects, there are two Dicer genes, Dicer-1 (Dcr-1) and Dicer-2 (Dcr-2), which are involved in the micro-RNA and small-interfering RNA pathways in many species, respectively. The function of Dicer in Plutella xylostella remains unknown. The full-length open reading frames of P. xylostella Dicer-1 (PxDcr-1) and Dicer-2 (PxDcr-2) were cloned and sequenced. Dcr-1andDcr-2 proteins shared similar structural domains with the Dicer-Partner Binding Domain (Dicer-PBD) and the double-strand RNA binding domain (dsRBD) present only in Dcr-1. The phylogenetic trees showed that lepidopteran Dcr-1s or Dcr-2s clustered in one branch, with PxDcr-1 in the basal position and PxDcr-2 closest to Plodia interpunctella Dicer. Two homozygous knockout lines, ΔPxDcr-1 and ΔPxDcr-2, were obtained by using the CRISPR-Cas9 technique. The ΔPxDcr-1 strain exhibited a high mortality rate, a low eclosion rate, a low egg-laying rate, a low hatching rate, and a shriveled ovariole without mature eggs. The ΔPxDcr-2 strain showed no significant difference from the wild-type in terms of survival, development and reproduction, but the RNA interference (RNAi) efficiency caused by dsRNA was significantly reduced. These findings demonstrate the involvement of PxDcr-1 in the development and reproduction of P. xylostella, specifically in the formation of ovarioles and eggs, and PxDcr-2 is indispensable for RNAi. These findings shed light on the function of Dcr-1 and Dcr-2 in Lepidoptera. © 2023 Society of Chemical Industry.

Profiling circulating microRNA and regulatory pathways in transfusion-dependent thalassemia and thalassemia trait compared to healthy controls: a preliminary study

Profiling circulating microRNA and regulatory pathways in transfusion-dependent thalassemia and thalassemia trait compared to healthy controls: a preliminary study

A Review of Potential Roles for Micro RNAs as Drugs Sensitivity Biomarkers in Breast Cancer

MiR-202, part of the let-7 family, plays a role in cell division and tumor development, especially in breast cancer (BC) among females. We have conducted a detailed review on new biomarkers to enhance BC screening and enable early diagnosis, particularly in younger women. Early detection and monitoring drug responses are crucial for optimal BC therapy, prompting the need for new biomarkers in diagnosis and prognosis. This review discusses recent findings on microRNAs in detecting, analyzing, and treating breast cancer (miRNA-BC). Although breast cancer patients often start treatment with radiotherapy, its effectiveness may decline with radiation resistance. This review study compares docetaxel-resistant breast cancer (DRBC) and docetaxel-sensitive cell lines, exploring the role of non-coding RNAs, especially circular RNAs (circRNAs), in DRBC development and identifying predictive biomarkers for taxane-containing therapies. MicroRNA sequencing and bioinformatics predict differences in microRNA expression, genes, and pathways between breast cancer cell types. Current evidence suggests that miR-202 dysregulation is linked to signaling pathways, influencing its anti- or pro-tumorigenic effects, showcasing its potential as a diagnostic biomarker.

Mechanisms of Honeysuckle Against Triple-negative Breast Cancer Based on Network Pharmacology and Molecular Docking

[Objective] To study the mechanism of action of the Honeysuckle against triple-negative breast cancer based on network pharmacology and molecular docking method, to provide a reference for elucidating its clinical anti-breast cancer mechanism. [Methods] The Honeysuckle active ingredients and their targets were screened by TCMSP and SwissTargetPrediction databases, and the target genes related to breast cancer were collected by GeneCards, OMIM and Disgenet databases, and the "Drug-Active Ingredient-Target-Disease" was constructed by using Cytoscape 3.9.1 software. The Cytoscape 3.9.1 software was used to construct a "drug-active ingredient-target-disease" network. The potential targets were imported into the STRING database to build a protein-protein interactions network (PPI). The core targets were annotated with the GO function and analyzed by KEGG pathway enrichment through the DAVID database. Molecular docking was carried out between the main active ingredients of the Honeysuckle and the potential targets through the Pymol software and AutoDock software. Molecular docking was performed using Pymol and AutoDock software. [A total of 23 active ingredients and 591 targets of the Honeysuckle, 1,811 triple-negative breast cancer disease targets, 186 potential targets, and 38 genes in the PPI network were screened in the two-component target databases, TCMSP and SwissTargetPrediction, and the three disease databases, GeneCards, OMIM, and Disgenet. In the PPI network, 38 key targets of the honeysuckle for breast cancer treatment were obtained, and after GO and KEGG analysis, 1,118 GO analysis results and 157 KEGG pathways were obtained. The GO analysis results showed that the honeysuckle's anti-breast cancer may be related to the transcription initiation process of the RNA polymerase II promoter, nuclear chromatin, DNA binding, etc.; the KEGG analysis results showed that the honeysuckle may be involved in the cancer pathway and the anti-breast cancer may involve the cancer pathway. The results of the KEGG analysis indicated that the honeysuckle anti-breast cancer might be involved in the cancer pathway, proteoglycan signaling pathway, microRNA pathway, thyroid hormone signaling pathway, etc. The molecular docking results showed that the predicted key components, quercetin and lignocerol, had better binding properties to the core targets, EP000, ERBB2, GAPDH, and MAPK3. [Conclusion] The anti-triple-negative breast cancer of the Honeysuckle mainly involves EP000, ERBB2, GAPDH , MAPK3 and 157 signaling pathways, and its active ingredients can inhibit the growth of tumor cells through multi-targets, multi-pathways, and multi-mechanisms.