Search Results (248)

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as pivotal regulators in both inflammatory and neoplastic skin disorders. Their implications in numerous biological processes, including gene expression, immune responses, and epidermal homeostasis, suggest potential applications as diagnostic and prognostic markers, as well as therapeutic targets. Methods: We conducted a literature search on lncRNAs involved in both psoriasis and cutaneous squamous cell carcinoma (cSCC), highlighting overlapping pathogenic mechanisms. Results: Several lncRNAs, such as HOTAIR, MALAT-1, H19, and uc.291, display dysregulated expression in both psoriasis and cSCC, influencing keratinocyte proliferation and apoptosis, immune modulation, cytokine signaling, and the synthesis of epidermal proteins. Conclusions: The intersection of lncRNA function in chronic inflammation and skin carcinogenesis underscores their role in mediating the transition from psoriatic inflammation to tumorigenesis, offering new insights into disease susceptibility; further investigation through functional studies and clinical validation are required. The study of lncRNA-mediated molecular pathways is particularly relevant given the increased risk of non-melanoma skin cancers and lymphoproliferative disorders among patients with chronic and severe forms of psoriasis. Full article

Uterine fibroids (leiomyomas) are benign tumors whose growth is influenced by estrogen and progesterone. This study aimed to compare the profiles of differentially expressed long non-coding RNAs (lncRNAs) in fibroids from postmenopausal and premenopausal women to identify hormone-responsive lncRNAs. RNA sequencing was performed on six pairs of fibroid (Fib) and adjacent myometrium (Myo) tissues from postmenopausal women. Out of 7876 normalized lncRNAs, 3684 were differentially expressed (≥1.5-fold), with 1702 upregulated and 1982 downregulated in Fib. Comparative analysis with a previously published premenopausal dataset identified 741 lncRNAs that were altered based on their menopausal status, including 62 lncRNAs that were uniquely dysregulated in postmenopausal samples. Overall, 9 lncRNAs were selected for validation by PCR in an expanded cohort of 31 postmenopausal and 84 premenopausal paired samples. Several lncRNAs, including LINC02433, LINC01449, SNHG12, H19, and HOTTIP, were upregulated in premenopausal Fib but not in postmenopausal ones, while ZEB2-AS1 displayed the opposite pattern. CASC15 and MIAT were elevated in Fib from both groups, although the increase was less pronounced in the postmenopausal group. LINC01117 was significantly downregulated in postmenopausal Fib, with no change observed in premenopausal samples. Additionally, analysis based on MED12 mutation status revealed that lncRNAs such as LINC01449, CASC15, and MIAT showed limited or reduced differential expression (mutation-positive vs. mutation-negative) in postmenopausal patients compared to the premenopausal group. These findings indicate that lncRNA expression in fibroids is modulated by menopausal status, likely reflecting hormonal influence. Hormone-responsive lncRNAs may play key roles in fibroid pathogenesis and represent potential targets for therapeutic intervention. Full article

The active form of vitamin D₃, 1,25(OH)₂D₃, exerts hierarchical control over gene expression, initially targeting transcription factors (TFs) that drive downstream responses. Here, we profile the transcriptional landscape of primary keratinocytes (HPEKp) and squamous cell carcinoma (SCC) cells in response to 1,25(OH)₂D₃, revealing a distinct shift in regulatory targets. While TFs accounted for 9.23% of differentially expressed genes (DEGs) in keratinocytes, this proportion dropped to 4.9% with prolonged exposure. In contrast, SCC cells displayed a five-fold reduction in TFs deregulation and a concurrent enrichment of long non-coding RNAs (lncRNAs), which comprised 22.25% of DEGs after 24 h treatment, with 81% upregulated. Integrative transcriptomic and in silico analyses showed that lncRNA induction was predominantly VDR-dependent, partially RXRA-dependent, and PDIA3-independent. Notably, 90% of deregulated lncRNAs were atypical for head and neck SCC. Several of these lncRNAs exhibit potential antitumor properties and may modulate SCC cell responsiveness to interferon-gamma (IFN-γ). In conclusion, these findings suggest that in SCC cells, the regulation of lncRNA expression—rather than transcription factor modulation—may represent a mechanism of the cellular response to 1,25(OH)₂D₃. Full article

Nucleobase and nucleoside analogs are critical components of antimetabolite chemotherapy treatments used to disrupt DNA replication and induce apoptosis in rapidly proliferating cancer cells. However, the development of resistance to these agents remains a major clinical challenge. This review explores the epigenetic mechanisms that contribute to acquired chemoresistance, focusing on DNA methylation, histone modifications, and non-coding RNAs (ncRNAs). These epigenetic alterations regulate key processes such as DNA repair, drug metabolism, cell transport, and autophagy, enabling cancer cells to survive and resist therapeutic pressure. We highlight how dysregulation of DNA methyltransferases (DNMTs) and histone acetyltransferases (HATs) modulates expression of transporters (e.g., hENT1, ABCB1), DNA repair enzymes (e.g., Polβ, BRCA1/2), and autophagy-related genes (e.g., CSNK2A1, BNIP3). Furthermore, emerging roles for long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in regulating nucleoside export and DNA damage response pathways underscore their relevance as therapeutic targets. The interplay of these epigenetic modifications drives resistance to agents such as gemcitabine and 5-fluorouracil across multiple tumor types. We also discuss recent progress in therapeutic interventions, including DNMT and HDAC inhibitors, RNA-based therapeutics, and CRISPR-based epigenome editing. Full article

LncRNAs, a type of RNAs exceeding 200 nucleotides (nt) and lacking representative open reading frames (ORFs), have emerged as crucial regulatory molecules that modulate numerous growth and development processes in plants. While substantial progress has been made in interpreting the functions and regulatory mechanisms of coding RNAs, the study of lncRNAs in Tibetan hulless barley remains incomplete. To elucidate the coordination of drought stress responses in Tibetan hulless barely by lncRNAs, we analyzed the previously published RNA-seq data from two cultivars of hulless barley, drought-tolerant (Z772) and drought-sensitive (Z013), subjected to varying durations of drought treatment (0, 1, and 5 h). Initially, we identified a total of 2877 lncRNAs through a strict pipeline, of which 2179 were co-expressed in both cultivars. Additionally, 331 and 367 lncRNAs showed cultivar-specific expression patterns in Z772 and Z013, respectively. Given the trans-regulatory functions of lncRNAs, we utilized WGCNA and uncovered 11 modules that were enriched in drought-responsive pathways. Within these modules, lncRNAs and neighboring PCGs were co-clustered in key control modules. The GO enrichment analysis of potential lncRNA-PCG pairs primarily involved processes related to the response to water deprivation, regulation of abiotic stress, and RNA metabolic processes. Notably, 12 high-confidence lncRNA-PCG pairs displayed concordant expression profiles, with some annotated as TFs. Two of these pairs were validated by qRT-PCR in the Tibetan hulless barley cultivar Kunlun 14. These findings suggested that lncRNAs may participate in regulatory networks involved in drought adaptation in Tibetan hulless barley, offering novel insights into the drought resistance mechanisms of Poaceae crops and potential targets for breeding drought-resistant varieties. Full article

Background: Endometrial receptivity is crucial for successful embryo implantation in assisted reproductive technologies (ARTs). MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have emerged as important post-transcriptional regulators of endometrial function, although their diagnostic and molecular functions are poorly understood. Methods: A systematic review was conducted following PRISMA 2020 principles and registered in PROSPERO (CRD420251001811). We looked at 28 peer-reviewed publications published between 2010 and 2025 that used endometrial tissue, blood, uterine fluid, saliva, and embryo culture medium to study miRNAs and other non-coding RNAs in endometrial receptivity, recurrent implantation failure (RIF), and infertility. Results: MiRNAs like miR-145, miR-30d, miR-223-3p, and miR-125b influence implantation-related pathways such as HOXA10, LIF-STAT3, PI3K-Akt, and Wnt/β-catenin. Dysregulated expression profiles were linked to inadequate decidualization, immunological imbalance, and poor angiogenesis. CeRNA networks that include lncRNAs (e.g., H19 and NEAT1) and circRNAs (e.g., circ_0038383) further regulate miRNA activity. Non-invasive biomarkers derived from plasma, uterine fluid, and embryo media showed high prediction accuracy for implantation outcomes. Conclusions: MiRNA signatures offer a functional and diagnostic blueprint for endometrial receptivity. This systematic review provides a timely and thorough synthesis of the existing literature, with the goal of bridging the gap between molecular discoveries and therapeutic applications. By emphasizing both the mechanistic importance and diagnostic value of certain miRNA signatures, it paves the way for future precision-based techniques in embryo transfer and endometrial assessment in ART. Full article

Prostate cancer (PCa) is the most frequently diagnosed malignancy in the male genitourinary tract. However, the regulatory mechanism of competitive endogenous RNAs (ceRNAs) in PCa remains unclear. In this study, we first performed immune scores of mRNA data from 481 PCa samples using single-sample Gene Set Enrichment Analysis (ssGSEA). Based on the immune scores, we then evaluated the tumor immune microenvironment and analyzed 28 types of immune cells in PCa, we constructed a comprehensive network with four lncRNAs (MEG3, PCAT1, SNHG19, TRG-AS1), three miRNAs (hsa-miR-488-3p, hsa-miR-210-5p, hsa-miR-137), and twenty-seven mRNAs (including H2AFJ, THBS1, HPGD). Among the 28 immune cell types, seven immune cell types were found to be significantly associated with clinical characteristics. These network nodes have prognostic significance in multiple cancers and play critical roles in malignancy development, indicating the network’s predictive capability. We also observed a strong correlation (r = 0.6) between T-helper type 1 (Th1) cells and lncRNA network modules. The network connectivity highlights the association between immune therapy biomarkers for PCa, particularly those related to H2AFJ, THBS1, and HPGD. These findings provide valuable insights into the ceRNA regulatory network and its implications for immune-based therapies in PCa. Full article

Adipocyte differentiation is a complex process in which pluripotent mesenchymal stem cells (MSCs) differentiate and develop into mature fat cells, also known as adipocytes. This process is controlled by various transcription factors, hormones, and signaling molecules that regulate the development of these cells. Recently, an increasing number of non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), have been established to be involved in the regulation of many biological processes, including adipocyte differentiation, development, metabolism, and energy homeostasis of white and brown adipose tissue. Several in vitro and in vivo studies reported the significant role of ncRNAs in either promoting or inhibiting adipocyte differentiation into white or brown fat cells by targeting specific transcription factors and regulating the expression of key adipogenic genes. Identifying the function of ncRNAs and their subsequent targets contributes to our understanding of how these molecules can be used as potential biomarkers and tools for therapies against obesity, diabetes, and other diseases related to obesity. This could also contribute to advancements in tissue-engineering based treatments. In this review, we intended to present an up-to-date comprehensive literature overview of the role of ncRNAs, including miRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), focusing particularly on miRNAs, in regulating the differentiation and development of cells into white and brown adipose tissue. In addition, we further discuss the potential use of these molecules as biomarkers for the development of novel therapeutic strategies for future personalized treatment options for patients. Full article

Long non-coding RNAs (lncRNAs) have been defined as non-coding transcripts exceeding 200 nucleotides, which play essential roles during transcriptional and post-transcriptional regulation in multiple biological processes. Understanding R. delavayi lncRNAs is of great significance as it is profoundly influenced by heat stress. In this research, a total of 1145 differentially expressed lncRNAs (DE-lncRNAs) and 9447 differentially expressed genes (DEGs) (log₂|FC| > 1, p < 0.05) were characterized between heat-stress-treated groups and control groups. Further analysis showed that 229 DE-lncRNAs (144 upregulated and 85 downregulated) were commonly distributed in two comparisons (CK_vs._H3 and CK_vs._H6). We further investigated the cis- and trans-acting genes of the upregulated DE-lncRNAs, and found that 142 upregulated DE-lncRNAs corresponded to 1565 cis-acting DEGs, and 143 upregulated DE-lncRNAs corresponded to 3417 trans-acting DEGs. KEGG enrichment analysis of these target genes revealed that cis- and trans-acting DEGs of upregulated DE-lncRNA were primarily enriched in five and twelve KEGG pathways, respectively. Co-expression network analysis of upregulated DE-lncRNAs and DEGs enriched in the common KEGG pathways revealed 57 co-expression relationships between 28 DE-lncRNAs and 43 cis-acting DEGs and 554 co-expression relationships between 26 DE-lncRNAs and 90 trans-acting DEGs. Six DE-lncRNAs and six of their target DEGs were used as candidate genes to verify the RNA-seq data using qRT-PCR. Further analysis revealed three target genes (TrxG, PEPC, and CCR) out of six candidate DEGs that were selected as candidate genes for subsequent research. This study examined the relationship between DE-lncRNAs and DEGs and further screened out candidate DE-lncRNAs that can potentially provide an important theoretical basis and experimental data for the genetic improvement of heat tolerance in R. delavayi. Full article

Insulin-like growth factors (IGFs) play crucial roles in the regulation of animal growth and reproduction. However, the functional and regulatory mechanisms underlying ovarian growth and oocyte maturation in teleosts remain unclear. In this study, the expression profiles of lncRNAs and mRNAs were analyzed in the ovaries of golden pompano (Trachinotus ovatus) treated with IGF1 and IGF2 proteins to gain insights into the role of these two IGF ligands in the regulation of ovarian development and maturation. A total of 1494 lncRNAs and 8728 mRNAs were differentially expressed following IGF1 treatment compared with the control group. A total of 101 lncRNAs and 377 mRNAs were differentially expressed after IGF2 treatment compared to those in the control group. The results revealed that KEGG pathways enriched by target genes of the DE lncRNAs overlapped significantly with those enriched by the DE mRNAs in both the IGF1 and IGF2 groups. The key overlapping enriched pathways included ECM receptor interaction, gap junction, Hedgehog signaling pathway, Ras signaling pathway, Rap1 signaling pathway, TGF beta signaling pathway, Wnt signaling pathway, GnRH signaling pathway, progesterone-mediated oocyte maturation, oocyte meiosis, cell cycle, and MAPK signaling pathway. The differentially expressed genes (DEGs) involved in ovarian development and oocyte maturation were cyp17a1, cyp19a1, star, hsd17b3, hsd17b7, adam23, slc26a6, htr2b, h2ax, nanos3, krt18, pgr, and inhbb, following IGF1 and IGF2 treatment. Furthermore, four lncRNAs (MSTRG.66521.1, MSTRG.49969.1, MSTRG.59923.1, and MSTRG.13767.1) for IGF1 and two (MSTRG.20896.2 and MSTRG.58123.2) for IGF2 within the lncRNA–mRNA network were found to target DEGs related to ovarian development and maturation. This suggests that IGFs may affect reproductive processes by regulating the expression of lncRNAs and mRNAs. RT-qPCR analysis revealed that these six lncRNAs showed high expression levels in the brain, pituitary, liver, and gonad tissues, indicating their potential involvement in regulating ovarian growth and development. This study elucidates the lncRNA–mRNA regulatory mechanism in response to IGF1 and IGF2 treatment during stage III of ovarian development in golden pompano, thereby deepening our understanding of its functional role. Full article

Genetic and epigenetic alterations of various biomolecules at the molecular level can contribute to the pathogenesis of hepatocellular carcinoma (HCC) and negative impact prognosis. In this study, we aimed to investigate the effects of von Willebrand factor (VWF) and ADAMTS13 on HCC prognosis, using bioinformatics tools. “These tools included GEPIA2, TIMER2, UALCAN database, KM-Plotter, TNM-plot, STRING, ENCORI, Human Protein Atlas, Targetscan 8.0, miRDB, Enrichr-KG, lncRNADisease and, GEO”. VWF expression levels were significantly upregulated in liver hepatocellular carcinoma (LIHC) tissues compared to healthy adjacent tissues. Conversely, ADAMTS13 expression levels were significantly downregulated in LIHC tissues compared with healthy adjacent tissues in GEPIA2 database. The upregulated expression of VWF was significantly associated with longer overall survival (OS). However, the downregulated expression of ADAMTS13 was not significantly related to OS. The promoter regions of VWF and ADAMTS13 were significantly hypomethylated. While a significant negative correlation was observed between VWF with CD4 + T cells, there was a positive correlation between VWF with CD8+ T cells. ADAMTS13 expression positively correlated with CD4+ T cells. Additionally, a positive correlation was observed between ADAMTS13 expression and long non-coding RNAs (lncRNAs) (H19, HOTAIR, MALAT1, and UCA1). Conversely, a negative correlation was observed between VWF expression and lncRNAs (H19, HOTAIR, MALAT1, and UCA1). Although these results are promising, they highlight the complexity of the interplay between VWF and ADAMTS13 in HCC progression. According to microarray data, while VWF expression levels were significantly downregulated, ADAMTS13 expression levels were significantly upregulated in HCC compared with the control in the GEO database. Further studies are needed to elucidate the mechanisms underlying these markers. Full article

Increasing evidence revealed that restoring the correct expression of lncRNAs could have implications in the management of melanoma patients. In this context, here, we aim to dissect the main characteristics of lncRNAs altered in melanoma and their crosstalk with the signaling pathways involved in the progression of this disease. We also highlight the role of nucleic acid-based techniques and natural compounds (i.e., phytochemicals) as a therapeutic tool to increase or silence their expression in cancer cells. Finally, we explore the advances in nanotechnologies as delivery systems to efficiently carry these chemicals into cancer cells, thus limiting their potential off-target effects. The analysis of the literature showed that HOTAIR, MALAT1, and H19 are the oncogenic lncRNAs most studied in melanoma, while MEG3 is an important tumor suppressor decreased in this cancer. The aberrant expression of these lncRNAs affects several hallmarks of cancer, e.g., proliferation, motility, and epithelial to mesenchymal transition, promoting the melanoma plasticity and drug resistance. In this frame, siRNA, antisense oligonucleotide, and CRISPR-Cas9 genome editing appear to be the most effective nucleic acid strategies to restore the physiologic expression of lncRNA, while curcumin, resveratrol, and quercetin are the main phytochemicals able to target and influence the expression of lncRNAs altered in cancer. Overall, this study provides a comprehensive overview regarding the role of lncRNAs in the phenotype plasticity of melanoma cells and their potential targeting using RNA-based therapy and natural products. Full article

Wound healing progresses through four phases: hemostasis, inflammation, proliferation, and remodeling. Wounds may become chronic if this process is disrupted. The use of small extracellular vesicle (sEV; EVs < 200 nm) exosomes (exo; ~40–120 nm) derived from human adipose stem cells (hASCs) as a treatment for wounds is well studied. The cargo of these exosomes is of great interest as this accelerates wound healing. Our previous studies identified lncRNAs GAS5 and MALAT1 as packaged and enriched in hASC exosomes. In this study, we use a rat model to examine the effects on wound healing when hASC exosomes are depleted of GAS5 and MALAT1. Rats were wounded and wounds were treated with 100 μg hASC_exo or hASC_exo-G-M every 2 days for 1 week. qPCR was completed to evaluate the molecular effects of depletion of GAS5 and MALAT1 from hASC_exo. RNAseq was performed on wound tissue to evaluate the molecular mechanisms changed by hASC_exo-G-M in wound healing. While hASC_exo-G-M significantly improved wound healing rate compared to control wounds, healing occurred slower than in wounds treated with hASC_exo that were not depleted of GAS5 and MALAT1. Overall, this study reveals that molecular functions associated with healing are reduced in the absence of GAS5 and MALAT1, highlighting the importance of these lncRNAs. Full article

Long noncoding RNAs (lncRNAs) are RNA molecules exceeding 200 nucleotides that do not encode proteins yet play critical roles in regulating gene expression at multiple levels, such as chromatin modification and transcription. These molecules are significantly engaged in cancer progression, development, metastasis, and chemoresistance. However, the function of lncRNAs in epithelial ovarian cancer (EOC) has not yet been thoroughly studied. EOC remains challenging due to its complex molecular pathogenesis, characterized by genetic and epigenetic alterations. Emerging evidence suggests that lncRNAs, such as XIST, H19, NEAT1, and MALAT1, are involved in EOC by modulating gene expression and signaling pathways, influencing processes like cell proliferation, invasion, migration, and chemoresistance. Despite extensive research, the precise mechanism of acting of lncRNAs in EOC pathogenesis and treatment resistance still needs to be fully understood, highlighting the need for further studies. This review aims to provide an updated overview of the current understanding of lncRNAs in EOC, emphasizing their potential as biomarkers and therapeutic targets. We point out the gaps in the knowledge regarding lncRNAs’ influence on epithelial ovarian cancer (EOC), deliberating on new possible research areas. Full article

Histone H3 trimethylated at lysine 4 (H3K4me3) is an histone mark associated with transcriptionally active genes. H3K4me3 has two types of distribution: a sharp distribution of approximately 500 bp and a broad H3K4me3 domain that may extend 4 kb and longer through the gene body. Most transcribed genes have a narrow H3K4me3 configuration, whereas genes involved in cell identity and tumor suppression have a broad arrangement in normal cells. In cancer cells, genes that promote cancer possess a broad H3K4me3 domain. In this study, we performed H3K4me3 chromatin immunoprecipitation sequencing to determine the genes with narrow and broad H3K4me3 configurations in normal colon epithelial cells and three colon cancer cell lines. The analysis revealed that genes involved in cell adhesion and nervous system development had an H3K4me3 peak next to their transcription start site in normal cells but not in colon cancer cells. Genes coding for long non-coding RNA (lncRNA) were differentially marked with a broad H3K4me3 domain in normal colon versus colon cancer cells (FENDRR in normal colon; ELFN1-AS1 in colon cancer). Identifying the genes that are silenced or activated, particularly in colon cancer, provides a list of actionable targets for designing effective treatments for this prevalent human disease. Full article