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Long non-coding RNAs (lncRNAs) have begun to receive overdue attention for their regulatory roles in gene expression and other cellular processes. Although most lncRNAs are lowly expressed and tissue-specific, notable exceptions include MALAT1 and its genomic neighbor NEAT1, two highly and ubiquitously expressed oncogenes with roles in transcriptional regulation and RNA splicing. Previous studies have suggested that NEAT1 is found only in mammals, while MALAT1 is present in all gnathostomes (jawed vertebrates) except birds. Here we show that these assertions are incomplete, likely due to the challenges associated with properly identifying these two lncRNAs. Using phylogenetic analysis and structure-aware annotation of publicly available genomic and RNA-seq coverage data, we show that NEAT1 is a common feature of tetrapod genomes except birds and squamates. Conversely, we identify MALAT1 in representative species of all major gnathostome clades, including birds. Our in-depth examination of MALAT1, NEAT1, and their genomic context in a wide range of vertebrate species allows us to reconstruct the series of events that led to the formation of the locus containing these genes in taxa from cartilaginous fish to mammals. This evolutionary history includes the independent loss of NEAT1 in birds and squamates, since NEAT1 is found in the closest living relatives of both clades (crocodilians and tuataras, respectively). These data clarify the origins and relationships of MALAT1 and NEAT1 and highlight an opportunity to study the change and continuity in lncRNA structure and function over deep evolutionary time.

Diabetic wound healing is a complex physiological process often hindered by the underlying metabolic dysfunctions associated with diabetes. Despite existing treatments, there remains a critical need to explore innovative therapeutic strategies to improve patient outcomes. This article comprehensively examines the roles of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating key phases of the wound healing process: inflammation, angiogenesis, reepithelialization, and tissue remodeling. Through a deep review of current literature, we discuss recent discoveries of ncRNAs that have been shown to either promote or impair the wound healing process in diabetic wound healing, which were not covered in earlier reviews. This review highlights the specific mechanisms by which these ncRNAs impact cellular behaviors and pathways critical to each healing stage. Our findings indicate that understanding these recently identified ncRNAs provides new insights into their potential roles in diabetic wound healing, thereby contributing valuable knowledge for future research directions in this field. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) play important roles in various biological progresses of carcinogenesis. However, the function of lncRNAs in human sinonasal squamous cell carcinoma (SNSCC) remains greatly unclear. In the current study, lncRNA AC091729.7 expression was examined in SNSCC samples by using microarray, RNA in situ hybridization (ISH) and real-time fluorescence quantitative PCR (qRT-PCR). Cell viability, colony-formation, wound-healing, and transwell assays were applied to SNSCC cells. Xenograft mouse models were employed to evaluate the role of AC091729.7 in growth of SNSCC in vivo. Human protein microarray (HuprotTM Protoarray) and RNA immunoprecipitation (RIP) were used for identifying AC091729.7 binding proteins in SNSCC. Results showed AC091729.7 was upregulated and closely connected with the survival of the SNSCC patients. Knockdown of AC091729.7 suppressed SNSCC cell migration, proliferation, invasion in vitro. Furthermore, downregulation of AC091729.7 could inhibit the growth of SNSCC in vivo. Moreover, Human protein microarray and RIP suggested that AC091729.7 directly combine with the serine/arginine rich splicing factor 2 (SRSF2). Our results suggest that in the cell progression of SNSCC, lncRNA AC091729.7 plays a carcinogenic role and serves as a novel biomarker and latent curative target in SNSCC patients. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the frequent tumors that seriously endanger the physical and mental well-being in women with strong heterogeneity, and its pathogenesis involves multiple risk factors. Depending on the type of BC, hormonal therapy, targeted therapy, and immunotherapy are the current systemic treatment options along with conventional chemotherapy. Despite significant progress in understanding BC pathogenesis and therapeutic options, there is still a need to identify new therapeutic targets and develop more effective treatments. According to recent sequencing and profiling studies, non-coding (nc) RNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation, and similarly, the expression of many ncRNAs is altered in breast cancer cell lines and tissues. The ability of single ncRNAs to regulate the expression of multiple downstream gene targets and related pathways provides a theoretical basis for studying them for cancer therapeutic drug development and targeted delivery. Therefore, it is far-reaching to explore the role of ncRNAs in tumor development and their potential as therapeutic targets. Here, our review outlines the potential of two major ncRNAs, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) as diagnostic and prognostic biomarkers as well as targets for new therapeutic strategies in breast cancer. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial infarction (AMI) is a cardiovascular disease with the highest morbidity and mortality rate in the world. Several studies have suggested that abnormal regulation of non-coding RNAs (ncRNAs) may play a vital role in the occurrence and progress of AMI. Objective: The purpose of this study was to investigate the clinical values of human leukocyte antigen complex group 11 (HCG11) or miR-532-3p in the diagnosis and prognosis of patients with AMI after percutaneous coronary intervention (PCI). Methods: The clinical data of 100 AMI patients who underwent PCI were analyzed retrospectively. According to whether major adverse cardiovascular events (MACE) occurred after PCI, they were divided into MACE group (n = 38) and non-MACE group (n = 62). Basic clinical data and serum HCG11 and miR-532-3p levels were analyzed. Multivariate Cox regression analysis was performed to evaluate the risk factors for MACE, and the receiver operator characteristic (ROC) curve was constructed to assess the clinical predictive value of HCG11 and miR-532-3p for MACE. Results: Compared with the control group, the serum HCG11 level and miR-532-3p in AMI patients were significantly increased or decreased, and the serum levels of HCG11 and miR-532-3p in the MACE group were significantly increased and decreased, compared with those in non-MACE group. Multivariate Cox regression showed that HCG11 and miR-532-3p were risk factors for MACE occurrence. ROC curve investigated that HCG11 combined with miR-532-3p has accurate predictive value for MACE. Conclusion: This study showed that serum HCG11 and miR-532-3p have certain predictive value for MACE after PCI in patients with AMI. Highlights: The serum levels of HCG11 and miR-532-3p in patients with AMI were significantly higher and lower than those in control group, respectively. Compared with the MACE group, the levels of HCG11 and miR-532-3p in the non-MACE group showed an increasing and decreasing trend. Multivariate regression analysis showed that high expression of HCG11 and low expression of miR-532-3p were risk factors for MACE. [ABSTRACT FROM AUTHOR]

Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients. [ABSTRACT FROM AUTHOR]

Breast cancer is a significant health challenge for women globally, including the Pakistani population. Numerous pathways and small molecules like noncoding ribonucleotides are implicated in breast cancer development and progression. Among these, lncRNAs, have garnered considerable attention due to their role in breast cancer tumorigenesis and metastasis. In the current study involving 52 mammary tumor samples from the Pakistani population, the expression of lncRNA MALAT1 (metastasis associated lung adenocarcinoma transcript 1) was studied via RT-PCR (Real-Time polymerase chain reaction). In addition, PI3K/AKT/mTOR pathway expression was also assessed through RT-PCR and immunohistochemistry in breast cancer patient samples. The study also investigated the cross-talk of lncRNA MALAT1 and PI3K pathway genes by inhibiting it with PI3K inhibitor (LY294002) in MDA-MB-231 cell line. Furthermore, lncRNA MALAT1 was silenced in MDA-MB-231 cells using siRNA to determine its impact on breast cancer proliferation and metastasis. The results revealed an upregulated expression of MALAT1 and PI3K/AKT/mTOR pathway genes in grade II and III breast tissue samples before chemotherapy. The proliferation, growth, and invasion of breast cancer cells were significantly reduced upon MALAT1 silencing in MDA-MB-231. Further, its downregulation substantially reduced the PI3K pathway expression levels at mRNA and protein levels. In conclusion, the current study suggests that MALAT1 could serve as a therapeutic target for breast cancer, underscoring its role in breast cancer proliferation and metastasis. Moreover, the study proposes a mechanism of action of MALAT1, demonstrating that its inhibition can reduce the expression of the PI3K/AKT/mTOR axis. These findings emphasize the potential significance of targeting MALAT1 as a therapeutic strategy for breast cancer, and further exploration of this interaction is warranted to gain deeper insight into the molecular mechanism of this lncRNA. [ABSTRACT FROM AUTHOR]

Uterine corpus endometrial carcinoma (UCEC), a prevalent kind of cancerous tumor in female reproductive system that has a dismal prognosis in women worldwide. Given the very limited studies of cuproptosis-related lncRNAs (CRLs) in UCEC. Our purpose was to construct a prognostic profile based on CRLs and explore its assess prognostic value in UCEC victims and its correlation with the immunological microenvironment.Methods: 554 UCEC tumor samples and 23 normal samples' RNA-seq statistics and clinical details were compiled from data in the TCGA database. CRLs were obtained using Pearson correlation analysis. Using LASSO Cox regression, multivariate Cox regression, and univariate Cox regression analysis, six CRLs are confirmed to develop a risk prediction model at last.We identified two main molecular subtypes and observed that multilayer CRLs modifications were related to patient clinicopathological features, prognosis, and tumor microenvironment (TME) cell infiltration characteristics, and then we verified the prognostic hallmark of UCEC and examined its immunological landscape.Finally, using qRT-PCR, model hub genes' expression patterns were confirmed. Results: A unique CRL signature was established by the combination of six differently expressed CRLs that were highly linked with the prognosis of UCEC patients. According to their CRLs signatures, the patients were divided into two groups: the low-risk and the high-risk groups. Compared to individuals at high risk, patients at low risk had higher survival rates (p < 0.001). Additionally, Cox regression reveals that the profiles of lncRNAs linked to cuproptosis may independently predict prognosis in UCEC patients. The 1-, 3-, and 5-year risks' respective receiver operating characteristics (ROC) exhibited AUC values of 0.778, 0.810, and 0.854. Likewise, the signature could predict survival in different groups based on factors like stage, age, and grade, among others. Further investigation revealed differences between the different risk score groups in terms of drug sensitivity,immune cell infiltration,tumor mutation burden (TMB) score and microsatellite instability (MSI) score. Compared to the group of high risk, the low-risk group had greater rates of TMB and MSI. Results from qRT-PCR revealed that in UCEC vs normal tissues, AC026202.2, NRAV, AC079466.2, and AC090617.5 were upregulated,while LINC01545 and AL450384.1 were downregulated. Conclusions: Our research clarified the relationship between CRLs signature and the immunological profile and prognosis of UCEC.This signature will establish the framework for future investigations into the endometrial cancer CRLs mechanism as well as the exploitation of new diagnostic tools and new therapeutic. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) is a highly prevalent type of cancer worldwide, and it is responsible for numerous deaths and cases of disease. Due to the diverse nature of this disease, it is necessary to conduct significant research that delves deeper into the molecular aspects, to potentially discover novel diagnostic and therapeutic approaches. Lately, there has been a significant increase in the focus on non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), due to their growing recognition for their involvement in the progression and manifestation of BCa. The interest in exosomes has greatly grown due to their potential for transporting a diverse array of active substances, including proteins, nucleic acids, carbohydrates, and lipids. The combination of these components differs based on the specific cell and its condition. Research indicates that using exosomes could have considerable advantages in identifying and forecasting BCa, offering a less invasive alternative. The distinctive arrangement of the lipid bilayer membrane found in exosomes is what makes them particularly effective for administering treatments aimed at managing cancer. In this review, we have tried to summarize different ncRNAs that are involved in BCa pathogenesis. Moreover, we highlighted the role of exosomal ncRNAs in BCa. [ABSTRACT FROM AUTHOR]

The long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) exhibits diverse and complicated functions in cancer progression. Despite reports suggesting both tumor-suppressive and oncogenic effects in various cancers, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study aimed to investigate the association between NEAT1 expression levels and survival outcomes in HNSCC patients. Paired tissue samples of tumor and non-cancerous matching tissues (NCMT) from 92 HNSCC patients were collected. NEAT1 expression was analyzed using RT-qPCR. Clinical characteristics, treatment received, and survival rates of the patients were assessed to determine the correlation with NEAT1 expression and explore its association with alcohol, betel quid, and cigarette use. Additionally, we examined the effect of arecoline on NEAT1 expression in normal human oral keratinocytes (NHOK) and fibroblasts (NHOF). The study revealed a significant downregulation of NEAT1 expression in oral cancer tissues compared to NCMT. Meanwhile, arecoline increased NEAT1 expression in NHOK and NHOF cells. However, patients with downregulated NEAT1 expression exhibited higher overall survival rates, particularly in those who did not receive chemotherapy or radiotherapy. NEAT1 expression levels are associated with survival outcomes in HNSCC patients, with upregulated expression indicating a worse prognosis, suggesting this lncRNA might contribute to cancer aggressiveness, especially in the absence of active treatment. These findings indicate NEAT1 may serve as a potential prognostic biomarker in HNSCC, but further research is required to elucidate its role in cancer progression and its potential as a therapeutic target. [ABSTRACT FROM AUTHOR]

Aims: The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non‐coding RNAs (lncRNAs) in EAT that might modulate HFpEF development. Methods: RNA sequencing (RNA‐seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real‐time PCR (qRT‐PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions. Results: HFpEF patients had higher EAT thickness and NT‐proBNP levels than the control group. A total of 64 471 transcripts were detected including 35 395 protein‐coding sequences, corresponding to 16 854 genes in EAT. RNA‐seq identified a total of 741 dysregulated mRNA transcripts (394 up‐regulated and 347 down‐regulated) and 334 differentially expressed lncRNA transcripts (222 up‐regulated and 112 down‐regulated) in the HFpEF group compared with the control group (P < 0.05). qRT‐PCR analysis confirmed that two lncRNAs ENST00000561775 (P = 0.0194) and ENST00000519093 (P = 0.027) and an mRNA POSTN (P = 0.003) were differentially expressed. Functional enrichment analysis of the differentially expressed mRNAs suggested their potential roles in immune response involving cytokine interaction and chemokine signalling. Conclusions: We are the first group to report on the lncRNA and mRNA landscape in EAT in HFpEF patients. Our study suggests the possible role of lncRNAs in EAT. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) are a distinct class of RNAs with longer than 200 base pairs that are not translated into proteins. Small Nucleolar RNA Host Gene 3 (SNHG3) is a lncRNA and frequently dysregulated in various human cancers. Objective: This review provides a comprehensive analysis of current research on lncRNA SNHG3, focusing on its role within the competitive endogenous RNA (ceRNA) network and its implications in cancer. Methods: A systematic literature review was conducted using PubMed up to October 2023. The search strategy included keywords such as "lncRNA SNHG3", "competitive endogenous RNA", "cancer", and related terms. Studies were selected based on relevance to SNHG3's involvement in cancer pathogenesis and progression. Results: Disruptions in the ceRNA network involving lncRNA SNHG3 can impair normal cell growth and differentiation, significantly contributing to disease pathogenesis, particularly cancer. This review highlights SNHG3's substantial impact on various cancer processes and its potential as a diagnostic and therapeutic tool for aggressive cancers. Conclusion: The findings underscore SNHG3's pivotal role in cancer prevention, diagnosis, and treatment, laying a foundation for future research in cancer management. Insights from this review emphasize the necessity for further exploration and development of SNHG3-based diagnostic and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Disulfidptosis, the newest form of programmed cell death, is closely associated with the immune microenvironment of cancer cells. Long non-coding RNA (lncRNA) has also been found to play a crucial role in melanoma. However, the role of disulfidptosis-related lncRNA in melanoma remains unclear. Through bioinformatic analysis of the transcriptional, clinical, and pathological data from the TCGA-SKCM (The Cancer Genome Atlas—Skin cutaneous melanoma) database, we established a 2-Disulfidptosis-related lncRNA (DRL) prognostic model and a novel molecular subtype for melanoma. The survival and ROC curves of the 2-DRL prognostic model demonstrated its strong efficacy in predicting the prognosis of melanoma. The high-risk group of melanoma exhibited a significant decrease in ESTIMATEScore, ImmuneScore, and StromalScore, indicative of pronounced immune suppression and exhaustion. Subgroup C2 of melanoma displayed an immune-activated state, while subgroups C1 and C3 showed immune suppression and exhaustion, potentially leading to poorer prognosis. Subgroup C1 demonstrated better sensitivity to Zoledronate, UMI-77, Nilotinib, and Cytarabine. Subgroup C2 exhibited greater sensitivity to Ribociclib, XAV939, Topotecan, and Ruxolitinib. Subgroup C3 showed higher sensitivity to VX-11e, Ulixertinib, Trametinib, and Afatinib. This study revealed the immune microenvironment status and targeted drug sensitivity in melanoma patients with different risk scores and molecular subtypes, offering valuable guidance for clinical treatment and identifying significant DRL targets for future in-depth research. [ABSTRACT FROM AUTHOR]

Among the most deadly malignancies that strike women worldwide, ovarian cancer is still one of the most common. The primary factor affecting a patient's survival is early lesion discovery. Unfortunately, because ovarian cancer is a sneaky illness that usually manifests as nonspecific symptoms only in advanced stages, its early detection and screening are challenging. A lot of research is being conducted on effective methods of diagnosing and treating ovarian cancer. Recently, non-coding RNAs (ncRNAs) have gained great popularity, which are considered to be the main regulators of many cellular processes, especially those occurring in cancer. LncRNAs are also being studied for their therapeutic use in the treatment of ovarian cancer and their use in diagnostics and as indicators of poor prognosis. In this article, we reviewed lncRNAs described in the literature that may play an important role in ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is the second most common age-related neurodegenerative disease after Alzheimer's. Pathogenic factors in Parkinson's include inflammation and oxidative stress, which lead to dopaminergic cell apoptosis. The case–control study aims to determine the expression level of long non-coding RNAs (lncRNAs) of the apoptosis pathway in Parkinson's patients compared to healthy individuals. In the case–control study, 50 patients with Parkinson's disease were examined, along with 50 healthy individuals matched in age and sex. In both groups, the expression of long non-coding RNAs, including taurine upregulated 1 (TUG1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), and growth arrest-specific 5 (GAS5), was compared using real-time polymerase chain reaction (PCR). Results: The ratio of MALAT1, NEAT1, and TUG1 gene expression in the case group was statistically significantly higher than in healthy individuals. The ratio of GAS5 gene expression in people with Parkinson's disease was lower, with a statistically significant difference. The ratio of HULC gene expression was higher in the case group, but it did not show a statistically significant difference with the control group. Conclusion: The involvement of long lncRNAs that increase apoptosis may play a role in the pathogenesis of the disease, which may be used for identification and therapeutic purposes. [ABSTRACT FROM AUTHOR]

Background: Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. Methods: Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. Results: The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. Conclusions: Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC. [ABSTRACT FROM AUTHOR]

Anoikis is a distinct type of programmed cell death and a unique mechanism for tumor progress. However, its exact function in gastric cancer (GC) remains unknown. This study aims to investigate the function of anoikis-related lncRNA (ar-lncRNA) in the prognosis of GC and its immunological infiltration. The ar-lncRNAs were derived from RNA sequencing data and associated clinical information obtained from The Cancer Genome Atlas. Pearson correlation analysis, differential screening, LASSO and Cox regression were utilized to identify the typical ar-lncRNAs with prognostic significance, and the corresponding risk model was constructed, respectively. Comprehensive methods were employed to assess the clinical characteristics of the prediction model, ensuring the accuracy of the prediction results. Further analysis was conducted on the relationship between immune microenvironment and risk features, and sensitivity predictions were made about anticancer medicines. A risk model was built according to seven selected ar-lncRNAs. The model was validated and the calibration plots were highly consistent in validating nomogram predictions. Further analyses revealed the great accuracy of the model and its ability to serve as a stand-alone GC prognostic factor. We subsequently disclosed that high-risk groups display significant enrichment in pathways related to tumors and the immune system. Additionally, in tumor immunoassays, notable variations in immune infiltrates and checkpoints were noted between different risk groups. This study proposes, for the first time, that prognostic signatures of ar-lncRNA can be established in GC. These signatures accurately predict the prognosis of GC and offer potential biomarkers, suggesting new avenues for basic research, prognosis prediction and personalized diagnosis and treatment of GC. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) mellitus is a chronic illness in children and teens, with rising global incidence rates. It stems from an autoimmune attack on pancreatic β cells, leading to insufficient insulin production. Genetic susceptibility and environmental triggers initiate this process. Early detection is possible by identifying multiple autoantibodies, which aids in predicting future T1D development. A new staging system highlights T1D's onset with islet autoimmunity rather than symptoms. Family members of T1D patients face a significantly increased risk of T1D. Italy recently passed a law mandating national T1D screening for pediatric populations. Measurements of β cell function continue to be essential in assessing efficacy, and different models have been proposed, but more appropriate biomarkers are mandatory for both progression studies before the onset of diabetes and during therapeutic monitoring. Biomarkers like microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) play key roles in T1D pathogenesis by regulating gene expression. Understanding their roles offers insights into T1D mechanisms and potential therapeutic targets. In this review, we summarized recent progress in the roles of some non-coding RNAs (ncRNAs) in the pathogenesis of T1D, with particular attention to miRNAs, lncRNAs, and circRNAs. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are versatile RNA molecules recently identified as key regulators of gene expression in response to environmental stress. Our primary focus in this study was to develop a robust computational pipeline for identifying structurally identical lncRNAs across replicates from publicly available bulk RNA-seq datasets. In order to demonstrate the effectiveness of the pipeline, we utilized the transcriptome of the thermophilic fungus Thermothelomyces thermophilus and assessed the expression pattern of lncRNAs in conjunction with Heat Shock Proteins (HSP), a well-known protein family critical for the cell's response to high temperatures. Our findings demonstrate that the identification of structurally identical transcripts among replicates in this thermophilic fungus ensures the reliability and accuracy of RNA studies, contributing to the validity of biological interpretations. Furthermore, the majority of lncRNAs exhibited a distinct expression pattern compared to HSPs. Our study contributes to advancing the understanding of the biological mechanisms comprising lncRNAs in thermophilic fungi. [ABSTRACT FROM AUTHOR]

Background: There is an association between obesity and psychological disorders such as depression, anxiety, and stress. Environmental factors and genetics play a crucial role in this regard. Several long non-coding RNAs (lncRNAs) are involved in the pathophysiology of the nervous system. Additionally, we intend to investigate how dietary glycemic index and load relate to psychological disorders in women with obesity and overweight by identifying the possible interaction with metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1). Methods: 267 overweight or obese women between the ages of 18 and 48 were recruited for the current study. A reliable and validated food frequency questionnaire (FFQ) consisting of 147 items assessed food consumption, glycemic load (GL), and glycemic index (GI). Depression-Anxiety-Stress Scales (DASS-21) were used to assess mental well-being. A real-time polymerase chain reaction (PCR) was used to assess transcript levels for lncRNAs MALAT1 and TUG1. Results: In obese and overweight women, a positive correlation was found between anxiety and MALAT1 mRNA levels (P = 0.007, CC = 0.178). Age, energy intake, physical activity, total fat, income, marriage, thyroid, and BMI were adjusted, and GI and TUG1 were positively correlated on DASS-21 (β = 0.006, CI = 0.001, 0.01, P = 0.031), depression (β = 0.002, CI = 0.001, 0.004, P = 0.019), Stress (β = 0.003, CI = 0.001, 0.005, P = 0.027). The interaction of GL and TUG1 on stress was also observed (β = 0.03, CI = 0.001, 0.07, P = 0.048). Conclusions: The lncRNA TUG1 appears to be associated with depression and stress through interaction with GI and correlated with stress by interaction with GL. To establish this concept, further research is required. [ABSTRACT FROM AUTHOR]

Background: Plant long non-coding RNAs (lncRNAs) have important regulatory roles in responses to various biotic and abiotic stresses, including light quality. However, no lncRNAs have been specifically linked to the Shade Avoidance Response (SAS). Results: To better understand the involvement of lncRNAs in shade avoidance, we examined RNA-seq libraries for lncRNAs with the potential to function in the neighbor proximity phenomenon in Arabidopsis thaliana (A. thaliana). Using transcriptomes generated from seedlings exposed to high and low red/far-red (R/FR) light conditions, we identified 13 lncRNA genes differentially expressed in cotyledons and 138 in hypocotyls. To infer possible functions for these lncRNAs, we used a 'guilt-by-association' approach to identify genes co-expressed with lncRNAs in a weighted gene co-expression network. Of 34 co-expression modules, 10 showed biological functions related to differential growth. We identified three potential lncRNAs co-regulated with genes related to SAS. T-DNA insertions in two of these lncRNAs were correlated with morphological differences in seedling responses to increased FR light, supporting our strategy for computational identification of lncRNAs involved in SAS. Conclusions: Using a computational approach, we identified multiple lncRNAs in Arabidopsis involved in SAS. T-DNA insertions caused altered phenotypes under low R/FR light, suggesting functional roles in shade avoidance. Further experiments are needed to determine the specific mechanisms of these lncRNAs in SAS. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs), once considered transcriptional noise, have emerged as critical regulators of gene expression and key players in cancer biology. Recent breakthroughs have revealed that certain lncRNAs can encode small open reading frame (sORF)-derived peptides, which are now understood to contribute to the pathogenesis of various cancers. This review synthesizes current knowledge on the detection, functional roles, and clinical implications of lncRNA-encoded peptides in cancer. We discuss technological advancements in the detection and validation of sORFs, including ribosome profiling and mass spectrometry, which have facilitated the discovery of these peptides. The functional roles of lncRNA-encoded peptides in cancer processes such as gene transcription, translation regulation, signal transduction, and metabolic reprogramming are explored in various types of cancer. The clinical potential of these peptides is highlighted, with a focus on their utility as diagnostic biomarkers, prognostic indicators, and therapeutic targets. The challenges and future directions in translating these findings into clinical practice are also discussed, including the need for large-scale validation, development of sensitive detection methods, and optimization of peptide stability and delivery. [ABSTRACT FROM AUTHOR]

Background and purpose: Long non-coding RNA (lncRNA) LINC01410, with a length of 647 bp, participates in a variety of tumor biological processes. However, the role and mechanism of LINC01410 involved in esophageal squamous cell carcinoma (ESCC) remain unclear. This study aimed to explore the potential mechanism of LINC01410 promoting ESCC proliferation and invasion, to provide a potential prognostic indicator and therapeutic target for individuals with ESCC. Methods: Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases were used to analyze the expression of LINC01410 and overall survival in esophageal squamous cell carcinoma data set in the Cancer Genome Atlas (TCGA). Gene Set Enrichment Analysis (GSEA) was performed to identify the underlying signaling pathways involved in the biological effects of LINC01410 in ESCC. A total of 62 pairs of ESCC tissues and paracancerous tissues from ESCC patients who underwent radical surgery in the Department of Thoracic Surgery at the First Affiliated Hospital of Xinxiang Medical College and the First People's Hospital of Pingdingshan City from January 2020 to December 2021 were collected. This project has been approved by the Hospital Ethics Committee (First Affiliated Hospital of Xinxiang Medical College, No. 2018036; First People's Hospital of Pingdingshan City, No. 2019-018). The expression of LINC01410 in ESCC tissues was detected by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). We transfected EC109 cells with LV-NC or LV-over/LINC01410 and EC9706 cells with shRNA-NC or shRNA-LINC01410. Stable transfected cells (EC109/NC, EC109/OE, EC9706/NC and EC9706/KD) were selected in primary cell culture medium containing puromycin. The expression of LINC01410 was detected by RTFQ-PCR. The impact of LINC01410 on ESCC cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. The effect of LINC01410 on ESCC cell invasion was detected by transwell migration assay. T cell factor/lymphoid enhancer factor 1 (TCF/LEF1) luciferase reporter assay was performed to validate the effect of LINC01410 on the activity of canonical Wnt/β-catenin signaling pathway. The expressions of Wnt/β-catenin and epithelial-mesenchymal transition (EMT) signal pathway related proteins in ESCC cells were detected by Western blot. Results: By analyzing the LINC01410 expression from ESCC samples in TCGA by GEPIA2, we found LINC01410 was consistently increased in ESCC tumors compared with normal tissues (P<0.05), and high LINC01410 expression was associated with poorer overall survival (OS). RTFQ-PCR assay showed that expressions of LINC01410 were higher in esophageal cancer tissues and esophageal cancer cells (EC109 and EC9706) than in precancerous tissues and HEEC cells (P<0.05). The expression level of LINC01410 was significantly correlated with invasion range, lymph node metastasis and TNM stage in ESCC patients (P<0.01). LINC01410 expression was also upregulated in EC109/OE, however the expression of LINC01410 in EC9706/KD was decreased (P<0.01). MTT assay showed overexpression of LINC01410 increased the viability of EC109 cells, while knockdown of LINC01410 decreased the viability of EC9706 cells (P<0.01). Colony formation assay indicated that overexpression of LINC01410 enhanced the clonogenic ability of ESCC cells, while knockdown of LINC01410 reduced colony formation (P <0.01). Transwell migration assay showed that LINC01410 overexpression drastically increased the number of migratory cells, while silencing of LINC01410 suppressed the migration in EC9706 cells (P<0.01). GSEA revealed that Wnt/β-catenin and EMT pathways were significantly enriched in ESCC samples with a high level of LINC01410. TCF/LEF1 luciferase reporter assay showed higher levels of Wnt-dependent activities were observed in EC109/OE cells, whereas silenced LINC01410 in EC9706 cells led to contrary results (P<0.01). Western blot analysis showed that overexpression of LINC01410 in EC109 cell significantly increased the expression levels of N-cadherin, β-catenin, cyclin D1, c-Myc and decreased E-cadherin expression, while knockdown LINC01410 resulted in opposite results. Conclusion: LINC01410 promotes proliferation and metastasis of ESCC, which might be caused by activation of Wnt/β-catenin and EMT signaling pathways. [ABSTRACT FROM AUTHOR]

Temperature is an important environmental factor affecting heading date of rice. Despite its importance, genes responsible for temperature-sensitive heading in rice have remained elusive. Our previous study identified a quantitative trait locus qHd1 which advances heading date under high temperatures. A 9.5-kb insertion was found in the first intron of OsMADS51 in indica variety Zhenshan 97 (ZS97). However, the function of this natural variant in controlling temperature sensitivity has not been verified. In this study, we used CRISPR/Cas9 to knock out the 9.5-kb insertion in ZS97. Experiments conducted under cotrolled conditions in phytotrons confirmed that deletion increased temperature sensitivity and advanced heading by downregulating the expression level of OsMADS51. One-hybrid assays in yeast, ChIP-quantitative polymerase chain reaction, electrophoretic mobility shift, and luciferase-based transient transactivation assays collectively confirmed that OsMADS51 affects heading date by regulation of heading date gene Ehd1. We further determined that the long non-coding RNA HEATINR is generated from the first intron of OsMADS51, offering an explanation for how the 9.5-kb insertion affects temperature sensitivity. We also found that OsMADS51 was strongly selected in early/late-season rice varieties in South China, possibly accounting for their strong temperature sensitivity. These insights not only advance our understanding of the molecular mechanisms underlying the temperature-responsive regulation of heading date in rice but also provide a valuable genetic target for molecular breeding. [ABSTRACT FROM AUTHOR]

Cardiac mesoderm enhancer-associated non-coding RNA (CARMN), an evolutionarily conserved long non-coding RNA (lncRNA), serves as the host gene for the miR143/145 cluster. It plays a crucial role in cardiovascular cell differentiation and the maintenance of vascular smooth muscle cell (VSMC) homeostasis, which are vital for normal physiological processes. Specifically, CARMN is associated with the pathological progression of cardiovascular diseases such as atherosclerosis, abdominal aortic aneurysm, and chronic heart failure. Moreover, it acts as a tumor suppressor in various cancers, including hepatocellular carcinoma, bladder cancer, and breast cancer, highlighting its potential as a beneficial biomarker and therapeutic target. This review provides a detailed examination of the roles of CARMN, its evolutionary conservation, expression patterns, and regulatory mechanisms. It also outlines its significant implications in the diagnosis, prognosis, and treatment of these diseases, underscoring the need for further translational research to exploit its clinical potential. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease that arises as a multi-stage process involving multiple cell types. Patients diagnosed with the same clinical stage and pathological classification may have different prognoses and therapeutic responses due to alterations in molecular genetics. As an essential marker for the molecular subtyping of breast cancer, long non-coding RNAs (lncRNAs) play a crucial role in gene expression regulation, cell differentiation, and the maintenance of genomic stability. Here, we developed a modular framework for lncRNA identification and applied it to a breast cancer cohort to identify novel lncRNAs not previously annotated. To investigate the potential biological function, regulatory mechanisms, and clinical relevance of the novel lncRNAs, we elucidated the genomic and chromatin features of these lncRNAs, along with the associated protein-coding genes and putative enhancers involved in the breast cancer regulatory networks. Furthermore, we uncovered that the expression patterns of novel and annotated lncRNAs identified in breast cancer were related to the hormone response in the PAM50 subtyping criterion, as well as the immune response and progression states of breast cancer across different immune cells and immune checkpoint genes. Collectively, the comprehensive identification and functional analysis of lncRNAs revealed that these lncRNAs play an essential role in breast cancer by altering gene expression and participating in the regulatory networks, contributing to a better insight into breast cancer heterogeneity and potential avenues for therapeutic intervention. [ABSTRACT FROM AUTHOR]

Background: Transposable elements (TEs) are major components of eukaryotic genomes. The extensive body of evidence suggests that although they were once considered "genomic parasites", transposons and their transcripts perform specific functions, such as regulation of early embryo development. Understanding the role of TEs in such parasites as trematodes is becoming critically important. Fasciola hepatica, a parasite affecting humans and livestock, undergoes a complex life cycle in diverse environments and hosts, and knowledge about its life cycle regulation is scarce so far. Methods: We summarized the data regarding the repetitive elements in F. hepatica and conducted bulk RNA-seq analysis across its life cycle stages. TE expression profiles were analyzed, focusing on differential expression and potential homology with previously described long non-coding RNAs (lncRNAs). Results: Differential expression analysis revealed stage-specific TE transcription patterns, notably peaking during egg and metacercariae stages. Some TEs showed homology with known lncRNAs and contained putative transcription factor binding sites. Interestingly, TE transcription levels were highest in eggs and metacercariae compared to adults, suggesting regulatory roles in trematode life cycle transitions. Conclusions: These findings suggest that TEs may play roles in regulating trematode life cycle transitions. Moreover, TE homology with lncRNAs underscores their significance in gene regulation. [ABSTRACT FROM AUTHOR]

Abstract Background Acute myocardial infarction (AMI) is a cardiovascular disease with the highest morbidity and mortality rate in the world. Several studies have suggested that abnormal regulation of non-coding RNAs (ncRNAs) may play a vital role in the occurrence and progress of AMI. Objective The purpose of this study was to investigate the clinical values of human leukocyte antigen complex group 11 (HCG11) or miR-532-3p in the diagnosis and prognosis of patients with AMI after percutaneous coronary intervention (PCI). Methods The clinical data of 100 AMI patients who underwent PCI were analyzed retrospectively. According to whether major adverse cardiovascular events (MACE) occurred after PCI, they were divided into MACE group (n = 38) and non-MACE group (n = 62). Basic clinical data and serum HCG11 and miR-532-3p levels were analyzed. Multivariate Cox regression analysis was performed to evaluate the risk factors for MACE, and the receiver operator characteristic (ROC) curve was constructed to assess the clinical predictive value of HCG11 and miR-532-3p for MACE. Results Compared with the control group, the serum HCG11 level and miR-532-3p in AMI patients were significantly increased or decreased, and the serum levels of HCG11 and miR-532-3p in the MACE group were significantly increased and decreased, compared with those in non-MACE group. Multivariate Cox regression showed that HCG11 and miR-532-3p were risk factors for MACE occurrence. ROC curve investigated that HCG11 combined with miR-532-3p has accurate predictive value for MACE. Conclusion This study showed that serum HCG11 and miR-532-3p have certain predictive value for MACE after PCI in patients with AMI.

Abstract Metformin, a widely used oral hypoglycemic drug, has emerged as a potential therapeutic agent for cancer treatment. While initially known for its role in managing diabetes, accumulating evidence suggests that metformin exhibits anticancer properties through various mechanisms. Several cellular or animal experiments have attempted to elucidate the role of non-coding RNA molecules, including microRNAs and long non-coding RNAs, in mediating the anticancer effects of metformin. The present review summarized the current understanding of the mechanisms by which non-coding RNAs modulate the response to metformin in cancer cells. The regulatory roles of non-coding RNAs, particularly miRNAs, in key cellular processes such as cell proliferation, cell death, angiogenesis, metabolism and epigenetics, and how metformin affects these processes are discussed. This review also highlights the role of lncRNAs in cancer types such as lung adenocarcinoma, breast cancer, and renal cancer, and points out the need for further exploration of the mechanisms by which metformin regulates lncRNAs. In addition, the present review explores the potential advantages of metformin-based therapies over direct delivery of ncRNAs, and this review highlights the mechanisms of non-coding RNA regulation when metformin is combined with other therapies. Overall, the present review provides insights into the molecular mechanisms underlying the anticancer effects of metformin mediated by non-coding RNAs, offering novel opportunities for the development of personalized treatment strategies in cancer patients.

Abstract Aims The molecular signatures in epicardial adipose tissue (EAT) that contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF) are poorly characterized. In this study, we sought to elucidate molecular signatures including genetic transcripts and long non‐coding RNAs (lncRNAs) in EAT that might modulate HFpEF development. Methods RNA sequencing (RNA‐seq) was performed to identify differentially expressed lncRNAs and mRNAs in EAT samples from patients with HFpEF (n = 5) and without HF (control, n = 5) who underwent coronary artery bypass grafting. The sequencing results were validated using quantitative real‐time PCR (qRT‐PCR). Bioinformatics analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of differentially expressed RNAs was performed to predict enriched functions. Results HFpEF patients had higher EAT thickness and NT‐proBNP levels than the control group. A total of 64 471 transcripts were detected including 35 395 protein‐coding sequences, corresponding to 16 854 genes in EAT. RNA‐seq identified a total of 741 dysregulated mRNA transcripts (394 up‐regulated and 347 down‐regulated) and 334 differentially expressed lncRNA transcripts (222 up‐regulated and 112 down‐regulated) in the HFpEF group compared with the control group (P

Background/purpose: The long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) exhibits diverse and complicated functions in cancer progression. Despite reports suggesting both tumor-suppressive and oncogenic effects in various cancers, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study aimed to investigate the association between NEAT1 expression levels and survival outcomes in HNSCC patients. Materials and methods: Paired tissue samples of tumor and non-cancerous matching tissues (NCMT) from 92 HNSCC patients were collected. NEAT1 expression was analyzed using RT-qPCR. Clinical characteristics, treatment received, and survival rates of the patients were assessed to determine the correlation with NEAT1 expression and explore its association with alcohol, betel quid, and cigarette use. Additionally, we examined the effect of arecoline on NEAT1 expression in normal human oral keratinocytes (NHOK) and fibroblasts (NHOF). Results: The study revealed a significant downregulation of NEAT1 expression in oral cancer tissues compared to NCMT. Meanwhile, arecoline increased NEAT1 expression in NHOK and NHOF cells. However, patients with downregulated NEAT1 expression exhibited higher overall survival rates, particularly in those who did not receive chemotherapy or radiotherapy. Conclusion: NEAT1 expression levels are associated with survival outcomes in HNSCC patients, with upregulated expression indicating a worse prognosis, suggesting this lncRNA might contribute to cancer aggressiveness, especially in the absence of active treatment. These findings indicate NEAT1 may serve as a potential prognostic biomarker in HNSCC, but further research is required to elucidate its role in cancer progression and its potential as a therapeutic target.

In eukaryotes, RNA molecules called long non-coding RNAs (LncRNAs) have been found. Molecules that exceed 200 base pairs in length are incapable of coding for proteins. Studying the function of LncRNAs in cancer has been the main focus of the current investigation, which has significantly impacted protein integrity and stability. LncRNAs can be regulated through various pathways, leading to chromatin changes and methylation or as miRNA sponges. The most common type of liver tumor worldwide is hepatocellular carcinoma (HCC), accounting for around 80 ​% of subjects. Nonetheless, the insufficiency of trustworthy molecular markers remains a significant challenge in HCC diagnosis and treatment evaluation. In HCC, LncRNAs such as MEG3, MALAT1, HULC, HOTAIR, and H19 dysregulation are closely associated with tumor expansion, metastasis, prognosis, and diagnosis. The primary goal of this investigation was to investigate the newly discovered roles and molecular mechanisms of LncRNAs in the pathophysiology of HCC cells to identify potential therapeutic targets.

Abstract Background Parkinson’s disease is the second most common age-related neurodegenerative disease after Alzheimer’s. Pathogenic factors in Parkinson’s include inflammation and oxidative stress, which lead to dopaminergic cell apoptosis. The case–control study aims to determine the expression level of long non-coding RNAs (lncRNAs) of the apoptosis pathway in Parkinson’s patients compared to healthy individuals. In the case–control study, 50 patients with Parkinson’s disease were examined, along with 50 healthy individuals matched in age and sex. In both groups, the expression of long non-coding RNAs, including taurine upregulated 1 (TUG1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), and growth arrest-specific 5 (GAS5), was compared using real-time polymerase chain reaction (PCR). Results The ratio of MALAT1, NEAT1, and TUG1 gene expression in the case group was statistically significantly higher than in healthy individuals. The ratio of GAS5 gene expression in people with Parkinson’s disease was lower, with a statistically significant difference. The ratio of HULC gene expression was higher in the case group, but it did not show a statistically significant difference with the control group. Conclusion The involvement of long lncRNAs that increase apoptosis may play a role in the pathogenesis of the disease, which may be used for identification and therapeutic purposes.

Abstract Background Long non-coding RNAs (lncRNAs) are a distinct class of RNAs with longer than 200 base pairs that are not translated into proteins. Small Nucleolar RNA Host Gene 3 (SNHG3) is a lncRNA and frequently dysregulated in various human cancers. Objective This review provides a comprehensive analysis of current research on lncRNA SNHG3, focusing on its role within the competitive endogenous RNA (ceRNA) network and its implications in cancer. Methods A systematic literature review was conducted using PubMed up to October 2023. The search strategy included keywords such as “lncRNA SNHG3”, “competitive endogenous RNA”, “cancer”, and related terms. Studies were selected based on relevance to SNHG3's involvement in cancer pathogenesis and progression. Results Disruptions in the ceRNA network involving lncRNA SNHG3 can impair normal cell growth and differentiation, significantly contributing to disease pathogenesis, particularly cancer. This review highlights SNHG3's substantial impact on various cancer processes and its potential as a diagnostic and therapeutic tool for aggressive cancers. Conclusion The findings underscore SNHG3's pivotal role in cancer prevention, diagnosis, and treatment, laying a foundation for future research in cancer management. Insights from this review emphasize the necessity for further exploration and development of SNHG3-based diagnostic and therapeutic strategies.

Abstract Disulfidptosis, the newest form of programmed cell death, is closely associated with the immune microenvironment of cancer cells. Long non-coding RNA (lncRNA) has also been found to play a crucial role in melanoma. However, the role of disulfidptosis-related lncRNA in melanoma remains unclear. Through bioinformatic analysis of the transcriptional, clinical, and pathological data from the TCGA-SKCM (The Cancer Genome Atlas—Skin cutaneous melanoma) database, we established a 2-Disulfidptosis-related lncRNA (DRL) prognostic model and a novel molecular subtype for melanoma. The survival and ROC curves of the 2-DRL prognostic model demonstrated its strong efficacy in predicting the prognosis of melanoma. The high-risk group of melanoma exhibited a significant decrease in ESTIMATEScore, ImmuneScore, and StromalScore, indicative of pronounced immune suppression and exhaustion. Subgroup C2 of melanoma displayed an immune-activated state, while subgroups C1 and C3 showed immune suppression and exhaustion, potentially leading to poorer prognosis. Subgroup C1 demonstrated better sensitivity to Zoledronate, UMI-77, Nilotinib, and Cytarabine. Subgroup C2 exhibited greater sensitivity to Ribociclib, XAV939, Topotecan, and Ruxolitinib. Subgroup C3 showed higher sensitivity to VX-11e, Ulixertinib, Trametinib, and Afatinib. This study revealed the immune microenvironment status and targeted drug sensitivity in melanoma patients with different risk scores and molecular subtypes, offering valuable guidance for clinical treatment and identifying significant DRL targets for future in-depth research.

Abstract Background Our previous study demonstrated that long intergenic noncoding RNA 02454 (LINC02454) may act as an oncogene to promote the proliferation and inhibit the apoptosis of papillary thyroid cancer (PTC) cells. This study was designed to investigate the mechanisms whereby LINC02454 is related to PTC tumorigenesis. Methods Thyroid cancer RNA sequence data were obtained from The Cancer Genome Atlas (TCGA) database. Weighted gene coexpression network analysis (WGCNA) was applied to identify modules closely associated with PTC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was used to identify the key pathways, and the maximal clique centrality (MCC) topological method was used to identify the hub genes. The Gene Expression Profiling Interactive Analysis (GEPIA) database was used to compare expression levels of key genes between PTC samples and normal samples and explore the prognostic value of key genes. The key genes were further validated with GEO dataset. Results The top 5000 variable genes were investigated, followed by an analysis of 8 modules, and the turquoise module was the most positively correlated with the clinical stage of PTC. KEGG pathway analysis found the top two pathways of the ECM − receptor interaction and MAPK signaling pathway. In addition, five key genes (FN1, LAMB3, ITGA3, SDC4, and IL1RAP) were identified through the MCC algorithm and KEGG analysis. The expression levels of the five key genes were significantly upregulated in thyroid cancer in both TCGA and GEO datasets, and of these five genes, FN1 and ITGA3 were associated with poor disease-free prognosis. Conclusions Our study identified five key genes and two key pathways associated with LINC02454, which might shed light on the underlying mechanism of LINC02454 action in PTC.

Alzheimer's disease (AD) is the most frequent type of dementia, presenting a substantial danger to the health and well-being of the aged population. It has arisen as a significant public health problem with considerable socioeconomic repercussions. Unfortunately, no effective treatments or diagnostic tools are available for Alzheimer's disease. Despite substantial studies on the pathophysiology of Alzheimer's, the molecular pathways underpinning its development remain poorly understood. Long non-coding RNAs (lncRNAs) vary in size from 200 nucleotides to over 100 kilobytes and have been found to play critical roles in various vital biological processes that play critical in developing Alzheimer's disease. This review intends to examine the functions of long non-coding RNAs in diagnosing and treating Alzheimer's disease and their participation in immunological responses associated with AD.

Abstract Background Plant long non-coding RNAs (lncRNAs) have important regulatory roles in responses to various biotic and abiotic stresses, including light quality. However, no lncRNAs have been specifically linked to the Shade Avoidance Response (SAS). Results To better understand the involvement of lncRNAs in shade avoidance, we examined RNA-seq libraries for lncRNAs with the potential to function in the neighbor proximity phenomenon in Arabidopsis thaliana (A. thaliana). Using transcriptomes generated from seedlings exposed to high and low red/far-red (R/FR) light conditions, we identified 13 lncRNA genes differentially expressed in cotyledons and 138 in hypocotyls. To infer possible functions for these lncRNAs, we used a ‘guilt-by-association’ approach to identify genes co-expressed with lncRNAs in a weighted gene co-expression network. Of 34 co-expression modules, 10 showed biological functions related to differential growth. We identified three potential lncRNAs co-regulated with genes related to SAS. T-DNA insertions in two of these lncRNAs were correlated with morphological differences in seedling responses to increased FR light, supporting our strategy for computational identification of lncRNAs involved in SAS. Conclusions Using a computational approach, we identified multiple lncRNAs in Arabidopsis involved in SAS. T-DNA insertions caused altered phenotypes under low R/FR light, suggesting functional roles in shade avoidance. Further experiments are needed to determine the specific mechanisms of these lncRNAs in SAS.

Abstract Long noncoding RNAs (lncRNAs) are versatile RNA molecules recently identified as key regulators of gene expression in response to environmental stress. Our primary focus in this study was to develop a robust computational pipeline for identifying structurally identical lncRNAs across replicates from publicly available bulk RNA-seq datasets. In order to demonstrate the effectiveness of the pipeline, we utilized the transcriptome of the thermophilic fungus Thermothelomyces thermophilus and assessed the expression pattern of lncRNAs in conjunction with Heat Shock Proteins (HSP), a well-known protein family critical for the cell’s response to high temperatures. Our findings demonstrate that the identification of structurally identical transcripts among replicates in this thermophilic fungus ensures the reliability and accuracy of RNA studies, contributing to the validity of biological interpretations. Furthermore, the majority of lncRNAs exhibited a distinct expression pattern compared to HSPs. Our study contributes to advancing the understanding of the biological mechanisms comprising lncRNAs in thermophilic fungi.

Abstract Background There is an association between obesity and psychological disorders such as depression, anxiety, and stress. Environmental factors and genetics play a crucial role in this regard. Several long non-coding RNAs (lncRNAs) are involved in the pathophysiology of the nervous system. Additionally, we intend to investigate how dietary glycemic index and load relate to psychological disorders in women with obesity and overweight by identifying the possible interaction with metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and taurine upregulated gene 1 (TUG1). Methods 267 overweight or obese women between the ages of 18 and 48 were recruited for the current study. A reliable and validated food frequency questionnaire (FFQ) consisting of 147 items assessed food consumption, glycemic load (GL), and glycemic index (GI). Depression-Anxiety-Stress Scales (DASS-21) were used to assess mental well-being. A real-time polymerase chain reaction (PCR) was used to assess transcript levels for lncRNAs MALAT1 and TUG1. Results In obese and overweight women, a positive correlation was found between anxiety and MALAT1 mRNA levels (P = 0.007, CC = 0.178). Age, energy intake, physical activity, total fat, income, marriage, thyroid, and BMI were adjusted, and GI and TUG1 were positively correlated on DASS-21 (β = 0.006, CI = 0.001, 0.01, P = 0.031), depression (β = 0.002, CI = 0.001, 0.004, P = 0.019), Stress (β = 0.003, CI = 0.001, 0.005, P = 0.027). The interaction of GL and TUG1 on stress was also observed (β = 0.03, CI = 0.001, 0.07, P = 0.048). Conclusions The lncRNA TUG1 appears to be associated with depression and stress through interaction with GI and correlated with stress by interaction with GL. To establish this concept, further research is required.

Abstract Long non-coding RNAs (lncRNAs), once considered transcriptional noise, have emerged as critical regulators of gene expression and key players in cancer biology. Recent breakthroughs have revealed that certain lncRNAs can encode small open reading frame (sORF)-derived peptides, which are now understood to contribute to the pathogenesis of various cancers. This review synthesizes current knowledge on the detection, functional roles, and clinical implications of lncRNA-encoded peptides in cancer. We discuss technological advancements in the detection and validation of sORFs, including ribosome profiling and mass spectrometry, which have facilitated the discovery of these peptides. The functional roles of lncRNA-encoded peptides in cancer processes such as gene transcription, translation regulation, signal transduction, and metabolic reprogramming are explored in various types of cancer. The clinical potential of these peptides is highlighted, with a focus on their utility as diagnostic biomarkers, prognostic indicators, and therapeutic targets. The challenges and future directions in translating these findings into clinical practice are also discussed, including the need for large-scale validation, development of sensitive detection methods, and optimization of peptide stability and delivery.

AIM: To characterize the N6-methyladenosine (m6A) modification patterns in long non-coding RNAs (lncRNAs) in sporadic congenital cataract (CC) and age-related cataract (ARC). METHODS: Anterior capsule of the lens were collected from patients with CC and ARC. Methylated RNA immunoprecipitation with next-generation sequencing and RNA sequencing were performed to identify m6A-tagged lncRNAs and lncRNAs expression. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and Gene Ontology annotation were used to predict potential functions of the m6A-lncRNAs. RESULTS: Large amount of m6A peaks within lncRNA were identified for both CC and ARC, while the level was much higher in ARC (49 870 peaks) than that in CC (18 688 peaks), yet those difference between ARC in younger age group (ARC-1) and ARC in elder age group (ARC-2) was quite slight. A total of 1305 hypermethylated and 1178 hypomethylated lncRNAs, as well as 182 differential expressed lncRNAs were exhibited in ARC compared with CC. On the other hand, 5893 hypermethylated and 5213 hypomethylated lncRNAs, as well as 155 significantly altered lncRNA were identified in ARC-2 compared with ARC-1. Altered lncRNAs in ARC were mainly associated with the organization and biogenesis of intracellular organelles, as well as nucleotide excision repair. CONCLUSION: Our results for the first time present an overview of the m6A methylomes of lncRNA in CC and ARC, providing a solid basis and uncovering a new insight to reveal the potential pathogenic mechanism of CC and ARC.

Background: Circular RNAs (Circ RNA) are a large class of non-coding RNAs which particularlystable RNAs and mostly originate from gene exons in animals. circRNAs are extremely abundantin the mammalian brains. They play role in the biological function and development of neurons.Nrf2 (nuclear factor erythroid 2–related factor 2) is a transcription factor that regulates cellularantioxidants and improves hippocampal synaptic plasticity, learning and memory. The aim ofthis study is the evaluation of Nrf2’s circRNA expression in the hippocampus of rats duringoxidative stress and the prediction of their function by bioinformatic tools. Methods: After evaluation of Nrf2’s circRNA prediction from circAtlas by BLAST, 3 out of 4sequences with high homology were selected and circ-Nrf2s expression was evaluated by qPCR,the interaction with micro RNAs and proteins was evaluated by miRDB, TargetScan, catRAPIDand HDOCK web server. Except control group, two groups of rats were treated with H2O2 (1%and 5%) then rats were sacrificed and hippocampal tissue was separated. qPCR was performedfor Nrf2 pathway gene expression and Nrf2 circRNAs. Then Circ-Nrf2-miRNA and 2circ-Nrf2-protein interaction were evaluated. Results: The most important circRNA that origin from Nrf2 is circ-Nrf2-1. Circ-Nrf2-1downregulates in oxidative stress and upregulates in 5% of H2O2 compared to 1%. However,linear Nrf2 was upregulated in both 1% and 5% H2O2. Circ-Nrf2-1 can bind to several miRNAsincluding miR-144-3p, miR-148a-5p, miR-155-5p. It also interacts with Celf1 which plays a rolein oxidative stress. Conclusion: According to results, it is plausible to suggest that circNrf2 may play a regulatoryrole in modulating oxidative stress.

Abstract Background Recent studies have shown that several long non-coding RNAs (lncRNAs) in the placenta are associated with preeclampsia (PE). However, the extent to which lncRNAs may contribute to the pathological progression of PE is unclear. Results Here, we report a hierarchical regulatory network involved in early-onset severe PE (EOSPE). We have carried out transcriptome sequencing on the placentae from patients and normal subjects to identify the differentially expressed genes (DEGs), including some lncRNAs (DElncRNAs). We then constructed a high-quality hierarchical regulatory network of lncRNAs, transcription factors (TFs), and target DEGs, containing 1851 lncRNA-TF interactions and 6901 TF-promoter interactions. The lncRNA-to-target regulatory interactions were further validated by the triplex structures between the DElncRNAs and the promoters of the target DEGs. The DElncRNAs in the regulatory network were clustered into 3 clusters, one containing DElncRNAs correlated with the blood pressure, including FLNB-AS1 with targeting 27.89% (869/3116) DEGs in EOSPE. We further demonstrated that FLNB-AS1 could bind the transcription factor JUNB to regulate a series members of the HIF-1 signaling pathway in trophoblast cells. Conclusions Our results suggest that the differential expression of lncRNAs may perturb the lncRNA-TF-DEG hierarchical regulatory network, leading to the dysregulation of many genes involved in EOSPE. Our study provides a new strategy and a valuable resource for studying the mechanism underlying gene dysregulation in EOSPE patients.

Abstract Background The escalating prevalence of metabolic diseases has led to a rapid increase in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (NASH-HCC). While oxaliplatin (OXA)-based hepatic arterial infusion chemotherapy (HAIC) has shown promise in advanced-stage HCC patients, its efficacy in NASH-HCC remains uncertain. This study aims to assess the effectiveness of OXA-based HAIC and elucidate the mechanisms underlying OXA resistance in NASH-HCC. Methods The key lncRNAs were screened through RNA-seq analysis of NASH/non-NASH and OXA-sensitive/OXA-resistant (OXA-S/R) HCC tissues. The biological functions of the lnc-OXAR (OXA resistance–related lncRNA in NASH-HCC) in NASH-HCC were verified through a series of in vitro and in vivo experiments. The molecular mechanism of lnc-OXAR was elucidated by fluorescence in situ hybridization, immunoprecipitation-mass spectrometry (FISH), Immunoprecipitation-Mass Spectrometry (IP-MS), RNA pulldown, RNA immunoprecipitation (RIP), methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and a dual-luciferase reporter assay. Results NASH-HCC exhibited reduced responsiveness to OXA-based HAIC compared to non-NASH HCC. We identified and validated a novel transcript namedlnc-OXAR, which played a crucial role in conferring OXA resistance to NASH-HCC. Inhibition of lnc-OXAR suppressed HCC cell growth and restored OXA sensitivity both in NASH-HCC mouse models and in vitro. Mechanistically, lnc-OXAR recruited Ku70 and cystatin A (CSTA), preventing Ku70 degradation and facilitating DNA double-strand break (DSB) repair, thereby promoting OXA resistance in NASH-HCC. Additionally, WTAP-mediated m6A modification enhanced the stability of lnc-OXAR in an IGF2BP2-dependent manner. Notably, silencing lnc-OXAR significantly enhanced the response to OXA in patient-derived xenograft (PDX) models derived from NASH-HCC. Conclusions The reduced responsiveness of NASH-HCC to OXA treatment can be attributed to the upregulation of lnc-OXAR. Our findings provide a rationale for stratifying HCC patients undergoing OXA-based HAIC based on etiology. Lnc-OXAR holds promise as a novel target for overcoming OXA resistance in NASH-HCC and improving prognosis.

The IgLON family of cell adhesion molecules consists of five members (LSAMP, OPCML, neurotrimin, NEGR1, and IgLON5) discovered as supporters of neuronal development, axon growth and guidance, and synapse formation and maintenance. Tumour suppression properties have recently been emerging based on antiproliferative effects through the modulation of oncogenic pathways. Available evidence endorses a role for non-coding RNAs or microRNAs as relevant controllers of IgLON molecule expression that can impact their critical physiological and pathological roles. Current findings support a function for long non-coding RNAs and microRNAs in the modulation of LSAMP expression in cell senescence, cancer biogenesis, addiction, and pulmonary hypertension. For OPCML, data point to a role for several microRNAs in the control of tumorigenesis. MicroRNAs were detected in neurotrimin-mediated functions in cancer biogenesis and in Schwann cell responses to peripheral nerve injury. For NEGR1, studies have mainly investigated microRNA involvement in neuronal responses to ischaemic injury, although data also exist about tumorigenesis and endothelial cell dysfunction. For IgLON5, information is only available about microRNA involved in myocardial infarction. In conclusion, despite much information being still missing and further research needed, the emerging picture favours a model in which non-coding RNAs exert a crucial role in modulating IgLON expression, ultimately affecting their important physiological functions.

Abstract Background Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML. Methods In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML. Results We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells. Conclusions Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.

Abstract Background Long non-coding RNAs (lncRNAs) are abundant and closely related to the occurrence and development of human diseases. LncRNAs are known to play a key role in many cardiovascular diseases. The purpose of this study was to investigate the effect of the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) on the degree of coronary artery lesions and prognosis in patients with coronary artery disease (CAD). Methods Patients who underwent coronary angiography (CAG) and dynamical-single photon emission computed tomography (D-SPECT) were selected as study subjects, and the results of CAG were reviewed, and the patients were grouped according to SYNTAX score. Evaluate the factors affecting SYNTAX scores. The follow-up analysis was conducted, and the endpoint events were major adverse cardiovascular events (MACEs). Kaplan–Meier method was used to estimate the survival rate, and multivariate Cox regression was used to analyze the relationship between RMRP and MACEs. Results The expression level of serum RMRP in patients with CAD was significantly higher than that in healthy people. Multivariate Logistic regression analysis showed that age, low-density lipoprotein cholesterol (LDL-C), RMRP and rest left ventricular ejection fraction (LVEF) were independent factors that affected SYNTAX scores. There were 19 cases of MACEs in the high RMRP group and 9 cases in the low RMRP group, and there was a significant difference in the MACE free survival curve between the two groups. Multivariate Cox regression analysis showed that age, SYNTAX score, rest LVEF and RMRP were risk factors for MACEs. Conclusions Serum RMRP is a key factor affecting the degree of coronary artery disease and prognosis in CAD patients.

Objective To investigate the expression of long non-coding RNA (lncRNA), surfactant associated 1 pseudogene (SFTA1P) in lung squamous carcinoma and its effect on the biological functions of SFTA1P in lung squamous carcinoma cell lines. Methods Based on the cancer genome atlas (TCGA) database, the differential expression of SFTA1P in tumor and normal tissues were compared in patients diagnosed with lung squamous cell carcinoma. Then, the expression of SFTA1P was detected in human normal lung epithelial cell line BEAS-2B and lung squamous cell lines SK-MES-1 and H520 with real-time quantitative polymerase chain reaction (RT-qPCR). SK-MES-1 and H520 cells with overexpression and/or knockdown of SFTA1P were constructed by transfecting the overexpression plasmids (pcDNA3.1-SFTA1P) and small interfering RNAs (si-SFTA1P-1 and si-SFTA1P-2). CCK-8 assay and Transwell assay were used to investigate the effect of SFTA1P on biological functions in lung squamous carcinoma cells. Differential gene expression analysis, correlation analysis and functional enrichment analysis were employed to explore the potential mechanism that SFTA1P may affect biological functions of lung squamous cells. Results Analysis of TCGA showed that the expression of SFTA1P was significantly lower in lung squamous cell carcinoma tissue than adjacent normal tissue (P

Abstract Background The coronavirus pandemic that started in 2019 has caused the highest mortality and morbidity rates worldwide. Data on the role of long non-coding RNAs (lncRNAs) in coronavirus disease 2019 (COVID-19) is scarce. We aimed to elucidate the relationship of three important lncRNAs in the inflammatory states, H19, taurine upregulated gene 1 (TUG1), and colorectal neoplasia differentially expressed (CRNDE) with key factors in inflammation and fibrosis induction including signal transducer and activator of transcription3 (STAT3), alpha smooth muscle actin (α-SMA), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in COVID-19 patients with moderate to severe symptoms. Methods Peripheral blood mononuclear cells from 28 COVID-19 patients and 17 healthy controls were collected. The real-time quantitative polymerase chain reaction (RT-qPCR) was performed to evaluate the expression of RNAs and lncRNAs. Western blotting analysis was also performed to determine the expression levels of STAT3 and α-SMA proteins. Machine learning and receiver operating characteristic (ROC) curve analysis were carried out to evaluate the distinguishing ability of lncRNAs. Results The expression levels of H19, TUG1, and CRNDE were significantly overexpressed in COVID-19 patients compared to healthy controls. Moreover, STAT3 and α-SMA expression levels were remarkedly increased at both transcript and protein levels in patients with COVID-19 compared to healthy subjects and were correlated with Three lncRNAs. Likewise, IL-6 and TNF-α were considerably upregulated in COVID-19 patients. Machine learning and ROC curve analysis showed that CRNDE-H19 panel has the proper ability to distinguish COVID-19 patients from healthy individuals (area under the curve (AUC) = 0.86). Conclusion The overexpression of three lncRNAs in COVID-19 patients observed in this study may align with significant manifestations of COVID-19. Furthermore, their co-expression with STAT3 and α-SMA, two critical factors implicated in inflammation and fibrosis induction, underscores their potential involvement in exacerbating cardiovascular, pulmonary and common symptoms and complications associated with COVID-19. The combination of CRNDE and H19 lncRNAs seems to be an impressive host-based biomarker panel for screening and diagnosis of COVID-19 patients from healthy controls. Research into lncRNAs can provide a robust platform to find new viral infection-related mediators and propose novel therapeutic strategies for viral infections and immune disorders.