Search Results (8,612)

Background/Objectives: The androgen receptor (AR)-driven transcriptional program plays a pivotal role in the development and progression of prostate cancer. The binding of androgen dihydrotestosterone (DHT) to AR initiates transcriptional activation, thereby altering the transcriptional landscape. DHT-induced long non-coding RNAs (lncRNAs) have been recognized as crucial players in prostate cancer pathogenesis. This study aims to identify and explore the important role of such lncRNAs in prostate cancer. Methods: This study first analyzed transcriptome data from an androgen-dependent cell line, LNCaP, treated with different DHT concentrations and found a batch of lncRNAs exhibiting DHT concentration dependence. TCGA data suggested a correlation between the DHT-induced lncRNA and prostate cancer. Finally, a series of in vivo and in vitro experiments confirmed the effect and mechanism of lncRNA in prostate cancer. Results: AC092718.4 was highly expressed in AR-positive prostate cancer cell lines and tissues, and its expression in patients with Gleason scores 6–9 was significantly higher than in a normal control group. Notably, the expression level of AC092718.4 was upregulated in a concentration-dependent manner with DHT. In vitro experiments revealed that overexpression of AC092718.4 promoted cell proliferation and inhibited cell apoptosis. Conversely, knockdown of AC092718.4 suppressed tumorigenesis in vivo. Furthermore, our investigation into the pathogenetic mechanism demonstrated that AC092718.4 could act as an miRNA sponge for miR-138-5p, attenuating its inhibitory effect on downstream oncogenes, such as FERMT2, RHOC, and HIF1A. These AC092718.4/miR-138-5p/mRNA axes, in turn, facilitated the progression of prostate cancer. Conclusions: For the first time, we demonstrate that AC092718.4 may function as an oncogenic factor in prostate cancer. The AC0927.8.4/miR-138-5p/mRNA axes potentially offer promising diagnostic and therapeutic targets for prostate cancer. Full article

Exposure to high-altitude hypoxia leads to complex physiological and molecular adaptations, particularly in skeletal muscle. MicroRNAs (miRNAs), including muscle-enriched (myomiRNAs) and hypoxia-responsive (hypoxamiRNAs), play critical roles in regulating these responses. We investigated miRNA expression changes in the skeletal muscle of healthy, non-smoking Italian adults (mean age 36.7 ± 12.4 years) participating in the Himalayan expedition “Lobuche Peak—Pyramid Exploration & Physiology” conducted in the Sagaramāthā (Mount Everest) National Park, Nepal. The peak overnight stay altitude was ≈5000 m at the Pyramid International Laboratory—Observatory. Muscle biopsies were taken before and after the expedition from Vastus lateralis, at one-third of the distance from the upper margin of the rotula to the anterior superior iliac spine. Small RNA sequencing was used to profile differentially expressed miRNAs. Several miRNAs were differentially expressed (exploratory analysis), suggesting potential involvement in hypoxia-related adaptation. These encompass both canonical myomiRNAs (e.g., miR-206, miR-486-5p) and hypoxamiRNAs (e.g., miR-378a-5p, miR-199a-3p, let-7b-5p). In enrichment analysis, we found several connections between miRNAs and pathways that may play a role in physiological regeneration or differentiation in muscle cells. Among functions, focal adhesion (p-value = 0.001), regulation of actin cytoskeleton (p-value = 0.026), Rap-1 (p-value = 0.007), cAMP (p-value = 0.017), MAPK (p-value = 0.019), and Hippo (p-value = <0.001) signaling pathways were predicted to be the most targeted. These findings provide preliminary insights into physiological adaptation, requiring confirmation in larger and controlled cohorts. Full article

Nuclear factor kappa B (NF-κB) signaling plays a central role in inflammation, immunity, cell survival, and cancer progression. Its constitutive activation is frequently observed in breast cancer, contributing to tumor growth, treatment resistance, and metastasis. MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression and may modulate NF-κB signaling in a subtype-specific or -independent manner. The aim of the study was to identify miRNAs that may potentially regulate the activity of genes associated with NF-κB signaling across five molecular subtypes of breast cancer in Polish women. Tumor and matched normal tissue samples were collected from 405 patients with five breast cancer subtypes: luminal A (n = 130), HER2-negative luminal B (n = 100), HER2-positive luminal B (n = 96), non-luminal HER2-positive (n = 36), and triple-negative breast cancer (TNBC, n = 43). Expression profile of selected NF-κB-related genes were evaluated using mRNA microarrays and RT-qPCR. Protein levels were assessed by ELISA. Candidate regulatory miRNAs were identified via miRNA microarrays and validated using the miRDB database. A consistent upregulation of MAP3K7, TAB2, TNFAIP3, CSNK2A1, BCL2L1, XIAP, CXCL2, and PLAU was observed across all subtypes, suggesting activation of canonical NF-κB signaling. Downregulation of specific miRNAs, miR-1297 and miR-30a (targeting MAP3K7), miR-134 (TAB2), miR-125b (TNFAIP3), and miR-4329 (XIAP), may contribute to this deregulation. For CSNK2A1, BCL2L1, CXCL2, and PLAU, no regulatory miRNAs meeting our criteria were identified. Our study reveals a subtype-independent activation of the canonical NF-κB signaling pathway in breast cancer, underpinned by consistent upregulation of key components (at both the transcript and protein levels. Dysregulation of specific miRNAs likely contributes to this altered gene expression. These findings suggest the presence of a common NF-κB-driven oncogenic program across molecular subtypes, with potential implications for developing miRNA-based therapeutic strategies targeting inflammation, survival signaling, and treatment resistance in breast cancer. Full article

The Kazakh horse represents a significant genetic resource within China’s equine population, characterized by notable resilience and an ability to thrive on coarse forage. Nevertheless, a decline in its numbers has been observed recently, making the improvement of its reproductive performance crucial for the preservation of this breed and the advancement of the related industry. In this study, testicular tissues from 1-year-old (pre-pubertal) and 2-year-old (post-pubertal) Kazakh horses were analyzed. miRNA sequencing was conducted on tissues from these age groups, followed by bioinformatics analyses to elucidate the functions of differentially expressed miRNAs (DEmiRNAs). The reliability of the sequencing data was subsequently verified using RT-qPCR. Analysis revealed 165 differentially expressed miRNAs (DEmiRNAs) in the testicular tissues between the two age groups. Of these, 118 DEmiRNAs (e.g., eca-miR-206 and eca-miR-2483) were significantly up-regulated (p < 0.05), and 47 DEmiRNAs (e.g., eca-miR-196a and eca-miR-211) were significantly down-regulated (p < 0.05). These DEmiRNAs were mainly implicated in biological processes including lipid metabolism and signal transduction. Their predicted target genes are potentially involved in key reproductive processes, notably testicular development and spermatogenesis. This study identifies candidate miRNAs and potential regulatory pathways associated with sexual maturation in Kazakh horses, providing a preliminary molecular basis for future functional validation and improvement of equine reproductive performance. Full article

Obstetrical diseases are complications associated with pregnancy or childbirth that can cause maternal sequelae and fetal complications. Among them, preeclampsia (PE) and preterm labor (PTL) are major causes of premature birth and are associated with an increased risk of cerebral palsy, developmental delay, and hearing impairment in infants. However, reliable diagnostic markers and therapeutic strategies for obstetrical diseases remain limited. The aim of this study was to investigate genes associated with obstetrical diseases and to evaluate the correlation between phosphocholine cytidylyltransferase 1 beta (PCYT1B) and miRNAs targeting PCYT1B for diagnostic analysis in PE and PTL. Using miRNA array analysis and luciferase assays, we identified PCYT1B, a key enzyme involved in phosphocholine metabolism in reproductive tissues, together with several candidate miRNAs targeting PCYT1B, including miR-3065-3p, miR-4660, miR-6752-5p, miR-6842-5p and miR-7110-5p. qRT-PCR analysis revealed a significant correlation between PCYT1B and these miRNAs in placental tissues from patients with PE and PTL (p < 0.05). Immunofluorescence staining further demonstrated that PCYT1B was localized in the syncytiotrophoblast layer of placental tissues, and its protein expression was consistent with mRNA expression levels. To investigate the functional role of these miRNAs, trophoblast cells were treated with miRNA mimics and inhibitors. These treatments significantly altered trophoblast invasion capacity and regulated the expression of migration-related genes, including RhoA, Rac1 and ROCK. Collectively, our findings suggest that miRNAs targeting PCYT1B may regulate trophoblast function and may play a key role in placental development and obstetrical diseases. These results indicate that PCYT1B and its regulatory miRNAs could serve as potential biomarkers for PE and PTL and may provide insights into the development of miRNA-based diagnostic strategies. Full article

Banana productivity is severely limited by drought, yet the molecular basis of drought adaptation and endophyte-mediated stress alleviation remains poorly understood. Here, we performed a genome-wide analysis of the SQUAMOSA promoter-binding protein-like (SPL) transcription factor family in Musa acuminata and examined their transcriptional responses to drought stress and Serendipita indica inoculation. We identified 38 MaSPL genes, all encoding proteins with the conserved SBP domain and predicted nuclear localization. Phylogenetic, motif, gene structure, and collinearity analyses indicated that MaSPL genes are evolutionarily conserved, unevenly distributed across chromosomes, and expanded primarily through segmental duplication under purifying selection. Promoter analysis showed several cis-acting elements and transcription factor binding sites related to light, phytohormone, and stress signaling. Ten MaSPL genes were predicted as putative targets of miR156. qRT-PCR analysis showed that drought stress markedly downregulated the tested MaSPL genes, whereas miR156a expression increased, supporting an inverse regulatory relationship. Under drought, S. indica inoculation enhanced expression of most tested MaSPLs, restoring transcript accumulation while reducing miR156a to near-basal levels. Notable responses were observed in members of the MaSPL2, MaSPL9, and MaSPL13, respectively. S. indica improves drought tolerance by enhancing antioxidant defenses, reducing oxidative stress, and preserving photosynthetic and osmotic stability. Taken together, our results demonstrate that S. indica confers drought resilience in banana by counteracting drought-induced repression of MaSPL genes via the miR156–SPL module and by strengthening key physiological defense mechanisms. Full article

Fine particulate matter (PM_2.5) can directly impact pulmonary epithelial cells, resulting in lung injury. While it is known that PM_2.5 can alter the expression profile of microRNAs in the lung, its specific role in damaging pulmonary epithelial cells remains unclear. This study, therefore, employed RT-qPCR, Western blotting, and dual luciferase reporter assays to investigate the regulatory role of microRNAs in PM_2.5-induced cellular damage. PM_2.5 exposure induces oxidative stress, autophagy, and ferroptosis in rat lung alveolar epithelial cells (RLE-6TN). Further functional rescue experiments confirm that the ferroptosis-specific inhibitor Fer-1 can block PM_2.5-induced ferroptosis. Bioinformatics analysis and validation indicate that miR-212-5p plays a crucial role by negatively regulating RASSF1 through targeted inhibition. Overexpression of miR-212-5p activates the PI3K/AKT signaling pathway, thereby promoting autophagy and ferroptosis. However, when the expression of both miR-212-5p and RASSF1 is suppressed, PM_2.5-induced autophagy and ferroptosis are significantly alleviated by inhibiting the PI3K/AKT/mTOR signaling pathway. Rescue validation experiments demonstrated that, under PM_2.5 exposure combined with RASSF1 overexpression, miR-212-5p exacerbates the aforementioned cellular damage process. This study reveals that miR-212-5p regulates autophagy and ferroptosis by targeting RASSF1. These findings provide a multi-target intervention strategy for PM_2.5-related lung diseases. Full article

Early detection remains the most decisive factor in improving outcomes for oral cancer and oral potentially malignant disorders. However, reliance on conventional biopsy-based pathways presents some practical and biological limitations. This scoping review aimed to map recent advances in non- and minimally invasive diagnostic approaches and to clarify how these innovations are being positioned within clinical workflows. Following PRISMA-ScR guidance, PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language original studies published between 2020 and 2025. Two independent reviewers screened and charted data on technologies, biomarkers, sampling sources, and clinical applications. Forty-nine studies were included. The literature clustered around four main domains: enhanced cytology (including liquid-based platforms and DNA ploidy analysis), multilayer liquid biopsy strategies (miRNA, cfDNA/ctDNA, methylation panels, and autoantibodies), optical and nanotechnology-based systems (Raman/SERS and sensor platforms), and artificial intelligence-driven decision support tools. Across modalities, a shared emphasis on rapid triage, risk stratification, and follow-up monitoring was evident. Nonetheless, variability in sampling, processing, analytical thresholds, and reporting standards limited cross-study comparability. Recent innovations point toward integrated, panel-based diagnostic models. Broader clinical adoption will require methodological standardization and robust multicenter validation. Full article

Yellow fever (YF) is an infectious disease caused by the yellow fever virus (YFV), an arbovirus of the Flaviviridae family. It is transmitted through the bite of infected mosquitoes of the Culicidae family and affects both humans and non-human primates (NHPs). This study aimed to investigate the sylvatic Culicidae fauna and the occurrence of natural YFV infection in a microregion of southern Santa Catarina, Brazil, an area recently affected by a sylvatic YF outbreak. Entomological collections were conducted between January and February 2023 in five municipalities with confirmed viral circulation. Natural YFV infection was assessed using RT-LAMP. A total of 4352 female culicids were collected, representing at least 32 species, including several key sylvatic YFV vectors. Haemagogus leucocelaenus was identified in all sampled municipalities, whereas Haemagogus (Haemagogus) janthinomys Dyar, 1921, historically considered the primary vector of sylvatic YFV in Brazil, was not detected. Mosquitoes from the genera Aedes Meigen, 1818; Haemagogus Williston, 1896; Psorophora Robineau-Desvoidy, 1827; and Sabethes Robineau-Desvoidy, 1827 were tested for YFV. Only one pool, composed of Sabethes albiprivus, tested positive, yielding a minimum infection rate (MIR) of 11.6. This is the first record of natural YFV infection in Sa. albiprivus in southern Brazil, and only the third record globally, highlighting its potential role as a secondary vector in maintaining viral circulation in sylvatic environments. Based on species presence and abundance, Hg. leucocelaenus is likely to have acted as the primary YFV vector in the study area. The composition of the culicid fauna, coupled with the detection of YFV in sylvatic vectors, indicates an ongoing epidemiological risk. These findings underscore the need to strengthen entomological surveillance and expand YF vaccination coverage in affected and neighbouring regions. Full article

Finite element modeling (FEM) of hybrid bonding stacks for high-density 3D integration suffers from excessive computational load and prohibitive simulation time. To address this critical technical bottleneck, this paper proposes an analytical lumped-distributed equivalent circuit model based on multi-layer structures. The model incorporates both redistribution layer (RDL) parasitics and metal–insulator–semiconductor (MIS) depletion effects for comprehensive signal integrity analysis. Frequency-dependent RLGC electromagnetic parameters were extracted from through-silicon via (TSV) and RDL interconnects. These parameters were numerically calculated using MATLAB R2020a to construct the equivalent circuit model in ADS. The model was subsequently validated against COMSOL finite element simulations. The results demonstrated that the proposed methodology achieved maximum deviations below 5% for all S-parameters in double-layer structures. For 5-layer stacks, errors were controlled within 10% across the 0–40 GHz frequency range. Computation time was reduced from several minutes to seconds. The proposed equivalent circuit method significantly reduces computational time while maintaining accuracy, providing an efficient simulation methodology for signal integrity analysis and verification of hybrid bonding stack structures. Compared to existing single-layer models, this work extends the modeling approach to multi-layer hybrid bonding stacks while comprehensively accounting for both RDL parasitics and MIS depletion effects, addressing a critical gap in the current state of the art. Full article

The advent of breast cancer molecular subtyping has transformed management, enabling treatment personalisation and de-escalation beyond traditional stage-based approaches. Established biomarkers, such as Ki-67 in luminal disease, HER2 amplification, and PD-L1 expression in triple-negative breast cancer, underpin seminal clinical trials yet remain imperfect predictors of response and long-term outcome. MicroRNAs have emerged as promising next-generation biomarkers and therapeutic tools. As master regulators of gene expression, both tumour-derived and circulating microRNAs can refine diagnosis and molecular subclassification, inform prognosis and therapeutic selection, act as treatment sensitisers, and potentially serve as direct therapeutic targets. Well-characterised miRNAs such as miR-221 have been implicated in endocrine resistance, while recent liquid-biopsy approaches have enabled the identification of circulating miR-145 and exosomal miR-155 as predictors of pathological complete response in HER2-positive disease. Their detectability in tissue, blood and other biofluids offers a minimally invasive means to dynamically monitor cancer behaviour and response, supporting more precise therapeutic decision-making. This review synthesises the current evidence for miRNA-based biomarkers across oestrogen-receptor positive, HER2-positive and triple-negative breast cancer and outlines their potential integration into biomarker-driven clinical trial designs and personalised treatment strategies. Full article

MicroRNAs (miRNAs) play important roles in the regulation of gene expression and are frequently dysregulated in cancer. Among them, the miR-196 family has been implicated in multiple malignancies, including colorectal cancer (CRC), but the isoform-specific transcriptional effects of miR-196A and miR-196B remain poorly understood. In this study, we generated miR-196A and miR-196B knockout SW48 CRC cell lines using CRISPR-based genome editing and performed RNA sequencing to investigate the transcriptional consequences of individual miR-196 isoform deletion. Transcriptomic analysis revealed widespread gene expression changes in both knockout models and demonstrated distinct clustering patterns between parental SW48 cells and miR-196-deficient cells. Functional enrichment analysis indicated that the altered genes were associated with biological processes related to cytoskeletal organization, intracellular transport, protein folding, and metabolic regulation. Notably, both shared and isoform-specific transcriptional alterations were observed, suggesting that miR-196A and miR-196B contribute to partially overlapping but distinct regulatory networks in CRC cells. Collectively, these findings provide a comprehensive transcriptomic overview of miR-196 isoform deletion in colorectal cancer cells and highlight potential isoform-dependent transcriptional programs that may contribute to CRC biology. Full article

Thyroid cancer is the most prevalent endocrine malignancy, and papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Although the prognosis is generally favorable, a better understanding of the molecular mechanisms involved in this pathology could lead to new treatment opportunities. Dysregulation of miRNA expression has been correlated with tumor development, and miR-1179 has been previously identified as one of the most downregulated miRNAs in PTC. This study aimed to explore the role of miR-1179 in thyroid tumorigenesis. miR-1179 was overexpressed in the TPC-1, B-CPAP, and HTori-3 thyroid cell lines to characterize its function and identify mRNA targets. The relevance of our data for human PTC was then addressed by analyzing TCGA and independent PTC. We showed that miR-1179 triggered apoptosis and inhibited cell migration. We identified ELF3 as a direct target of miR-1179 and other effectors, including NOTCH3 and CX3CL1. Finally, we revealed the existence of an inverse correlation between decreased expression of miR-1179 and increased expression of ELF3, NOTCH3, and CX3CL1 mRNA in human PTC. Our findings suggest that miR-1179 is a tumor suppressor gene and that its loss may contribute to thyroid tumor progression by promoting the expression of ELF3, NOTCH3, and CX3CL1. Full article

Lysosomes are crucial for the function of fetal vacuolated enterocytes in neonatal piglets, yet how they are regulated by miRNAs remains poorly defined. Therefore, this study aimed to elucidate how miRNAs govern lysosomal homeostasis in the developing intestine. Using a neonatal piglet model of lysosomal dysfunction induced by imipramine (IMI), we identified ssc-miR-214-3p as a key down-regulated miRNA implicated in lysosomal pathways. In IPEC-J2 enterocytes, the miR-214-3p mimic ameliorated IMI cytotoxicity by restoring cell viability and migration while suppressing apoptosis. Further analysis revealed that miR-214-3p directly reversed the lysosomal defects triggered by IMI treatment. Specifically, it alleviated lysosomal alkalinization and markedly restored acid phosphatase (ACP) activity, indicating a recovery of the acidic hydrolytic environment. This restoration was also accompanied by the preservation of lysosomal membrane integrity and a consequent reduction in the nuclear translocation of transcription factor EB (TFEB). Furthermore, cathepsin D (CTSD) was validated as a direct target of miR-214-3p by luciferase assay, and its overexpression reversed the protective effects of the mimic on lysosomal acidification and lysosome-associated membrane protein 1 (LAMP1) levels. Collectively, our findings reveal a novel miR-214-3p/CTSD axis that regulates lysosomal homeostasis during neonatal intestinal maturation, providing a potential therapeutic target for porcine intestinal disorders. Full article

Chicken coccidiosis, a severe intestinal parasitic disease caused by Eimeria protozoa, causes substantial annual economic losses to the global poultry industry. This study focused on investigating the role of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) in modulating chicken innate immune responses against Eimeria tenella (E. tenella) infections. Here, we show that TRAF6 is sensitive to the process of E. tenella infection, and cecal tissue responds to the early infection of E. tenella by up-regulating the expression of TRAF6. Specifically, TRAF6 overexpression enhances E. tenella-induced activation of the NF-κB pathway (a core innate immune signaling cascade), thereby promoting host inflammatory cytokines production and cell apoptosis, while TRAF6 knockdown mitigates these pathological effects. Mechanistically, TRAF6-mediated regulation of NF-κB pathway activation and inflammatory responses during E. tenella infection can be specifically targeted by key microRNAs (miRNA), gga-miR-7b, in chickens. Taken together, this study identifies that TRAF6 plays an important regulatory role in innate immune response against E. tenella infection, providing novel insights into host–parasite interactions and potential targets for coccidiosis control. Full article