Search Results (75)

Background: Long non-coding RNAs (lncRNAs) are crucial factors affecting the occurrence, progression, and prognosis of gastric carcinoma (GC). The accumulation of disulfide bonds to excessive levels in cells expressing high SLC7A11 triggers disulfidptosis, which functions as a regulated form of cellular death. Research has demonstrated that upregulated SLC7A11 is common in human cancers, but the effect of disulfidptosis on GC remains unclear. Identifying lncRNAs associated with disulfidptosis (drlncRNAs) and establishing a prognostic risk profile holds considerable importance for advancing GC research and treatment. Methods: Clinical records and transcriptomic datasets from individuals with GC were acquired from The Cancer Genome Atlas (TCGA) repository. A three-drlncRNA risk model was built using three common regression analysis methods. Then we used receiver operating characteristic (ROC) curves, independent prognostic analysis, and additional statistical approaches to assess the precision of the model. This investigation additionally encompassed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, immune cell infiltration evaluation, and pharmacological sensitivity predictions. To further investigate immunotherapy response disparities between patient cohorts with elevated- and reduced-risk scores, analyses of tumor mutational burden (TMB), tumor immune dysfunction and exclusion (TIDE), and microsatellite instability (MSI) were implemented. Results: We constructed a unique model composed of three drlncRNAs (AC107021.2, AC016394.2, and AC129507.1). Its independent prognostic capability for GC patients was validated through both single-variable and multivariable Cox regression analyses. GO and KEGG pathway assessments revealed predominant enrichment within the elevated-risk cohort, particularly in pathways involving sulfur compound interactions, traditional Wnt signaling mechanisms, cell-substrate adherens junctions, and cAMP signaling cascades, among others. Tumor microenvironment (TME) evaluation demonstrated elevated ImmuneScores, StromalScores, and ESTIMATEScores within the high-risk patient population. Concurrently, this elevated-risk cohort exhibited enhanced immune cell infiltration patterns, whereas the reduced-risk group displayed superior expression of immune checkpoints (ICPs). Additional investigations revealed that patients categorized into the reduced-risk classification possessed greater tumor mutational burden, increased MSI-high proportions, and diminished tumor immune dysfunction and exclusion scores compared to their high-risk counterparts. Pharmacological sensitivity assessments confirmed the superior efficacy of several therapeutic agents, including gemcitabine and veliparib (ABT.888), in patients with lower risk classifications. Conclusions: Our established risk stratification system demonstrates independent prognostic predictive capacity while offering personalized clinical intervention guidance for individuals diagnosed with GC. Full article

Objective: This study aims to develop a prognostic model based on senescence-related long non-coding RNAs (lncRNAs) to predict the prognosis of patients with colon cancer and enhance their survival rates. Method: Differential expression analysis and Pearson correlation were employed to identify senescence-related lncRNAs in colon cancer. A risk prognosis model was constructed using univariate Cox regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The reliability of this model was validated through survival analysis, receiver operating characteristic (ROC) curves, bar charts, and calibration curves. Additionally, the relationship between the prognostic model, immune microenvironment, and drug sensitivity was explored. Results: A risk prognosis model comprising eight senescence-related lncRNAs (LINC02257, AL138921.1, ATP2B1-AS1, AC005332.7, AC007728.3, AC018755.4, AL390719.3, and THCAT158) was successfully established, demonstrating strong performance in predicting the overall survival rates of colon cancer patients (AUC = 0.733). A significant correlation was observed between the senescence-related lncRNA prognostic model and the tumor microenvironment, immune cell infiltration, and drug sensitivity (p < 0.05). Conclusions: The senescence-related lncRNA prognostic model developed in this work can accurately forecast the prognosis of colon cancer patients, offering new insights for personalized treatment approaches in colon cancer. Full article

In this study, we employed a total of eight distinct modifications of histone proteins (H3K23ac, H3K27me3, H3K36me3, H3K4me3, H3K9ac, H3K9me3, H4K12ac, and H4K20me1) to discern the various chromatin colors encompassing lncRNA genes in both mature and immature gonads of the human parasite Schistosoma mansoni. Our investigation revealed that these chromatin colors exhibit a tendency to aggregate based on the similarities in their metagene shapes, leading to the formation of less than six distinct clusters. Moreover, these clusters can be further grouped according to their resemblances by shape, which are co-linear with specific regions of the genes, and potentially associated with transcriptional stages. Full article

Aberrant DNA methylation plays a crucial role in breast cancer progression by regulating gene expression. However, the regulatory pattern of DNA methylation in long noncoding RNAs (lncRNAs) for breast cancer remains unclear. In this study, we integrated gene expression, DNA methylation, and clinical data from breast cancer patients included in The Cancer Genome Atlas (TCGA) database. We examined DNA methylation distribution across various lncRNA categories, revealing distinct methylation characteristics. Through genome-wide correlation analysis, we identified the CpG sites located in lncRNAs and the distally associated CpG sites of lncRNAs. Functional genome enrichment analysis, conducted through the integration of ENCODE ChIP-seq data, revealed that differentially methylated CpG sites (DMCs) in lncRNAs were mostly located in promoter regions, while distally associated DMCs primarily acted on enhancer regions. By integrating Hi-C data, we found that DMCs in enhancer and promoter regions were closely associated with the changes in three-dimensional chromatin structures by affecting the formation of enhancer–promoter loops. Furthermore, through Cox regression analysis and three machine learning models, we identified 11 key methylation-driven lncRNAs (DIO3OS, ELOVL2-AS1, MIAT, LINC00536, C9orf163, AC105398.1, LINC02178, MILIP, HID1-AS1, KCNH1-IT1, and TMEM220-AS1) that were associated with the survival of breast cancer patients and constructed a prognostic risk scoring model, which demonstrated strong prognostic performance. These findings enhance our understanding of DNA methylation’s role in lncRNA regulation in breast cancer and provide potential biomarkers for diagnosis. Full article

As a novel discovered mechanism of cell death, cuproptosis is copper-dependent and induces protein toxicity related to advanced tumors, disease prognosis, and human innate and adaptive immune response. However, it has not yet been fully established how the prognosis of lung adenocarcinoma (LUAD) is related to the immune microenvironment of cuproptosis-related lncRNAs using several bioinformatic techniques. In the study, 19 genes related to cuproptosis were collected. Subsequently, 783 lncRNAs related to the co-expression of cuproptosis were obtained. Moreover, the Cox model revealed and constructed four lncRNA (AC012020.1, AC114763.1, AL161431.1, AC010260.1) prognostic markers related to cuproptosis. Based on the median risk score (RS) values, patients were categorized into two groups: high risk and low risk. The Kaplan–Meier (KM) survival curve depicted a statistically significant overall survival (OS) rate among two groups. Principal component analysis (PCA) and receiver operator characteristic curve (ROC) proved that the model had promising ability in prognosis. The analysis of univariate and multivariate Cox regression revealed that RS served as an independent prognostic factor. Moreover, multivariate Cox regression was employed for the establishment of a nomogram of prognostic indicators. The tumor mutational burden (TMB) depicted a considerable difference between the two risk groups. The immunotherapy response of LUAD patients with high risk was improved compared to low risk patients. The study also revealed that drug sensitivity associated with LUAD was significantly linked to RS. The findings could be helpful to establish a good diagnosis, prognosis, and management regime for patients with LUAD. Full article

Tuberculosis (TB) is the leading cause of death among people with HIV-1 infection. To improve the diagnosis and treatment of HIV-TB patients, it is important to understand the mechanisms underlying these conditions. Here, we used an integrated genomics approach to analyze and determine the lncRNAs that are dysregulated in HIV-TB patients and HIV-TB patients undergoing anti-retroviral therapy (ART) using a dataset available in the public domain. The analyses focused on the portion of the genome transcribed into non-coding transcripts, which historically have been poorly studied and received less focus. This revealed that Mtb infection in HIV prominently up-regulates the expression of long non-coding RNA (lncRNA) genes DAAM2-AS1, COL4A2-AS1, LINC00599, AC008592.1, and CLRN1-AS1 and down-regulates the expression of lncRNAs AC111000.4, AC100803.3, AC016168.2, AC245100.7, and LINC02073. It also revealed that ART down-regulates the expression of some lncRNA genes (COL4A2-AS1, AC079210.1, MFA-AS1, and LINC01993) that are highly up-regulated in HIV-TB patients. Furthermore, the interrogation of the genomic regions that are associated with regulated lncRNAs showed enrichment for biological processes linked to immune pathways in TB-infected conditions. However, intriguingly, TB patients treated with ART showed completely opposite and non-overlapping pathways. Our findings suggest that lncRNAs could be used to identify critical diagnostic, prognostic, and treatment targets for HIV-TB patients. Full article

During the secretory phase of the menstrual cycle, endometrial fibroblast cells begin to change into large epithelial-like cells called decidual cells in a process called decidualization. This differentiation continues more broadly in the endometrium and forms the decidual tissue during early pregnancy. The cells undergoing decidualization as well as the resulting decidual cells, support successful implantation and placentation during early pregnancy. This study was carried out to identify new potentially important long non-coding RNA (lncRNA) genes that may play a role in human endometrial stromal fibroblast cells (hESF) undergoing decidualization in vitro, and several were found. The expression of nine was further characterized. One of these, AC027288.3, showed a dramatic increase in the expression of hESF cells undergoing decidualization. When AC027288.3 expression was targeted, the ability of the cells to undergo decidualization as determined by the expression of decidualization marker protein-coding genes was significantly altered. The most affected markers of decidualization whose expression was significantly reduced were FOXO1, FZD4, and INHBA. Therefore, AC027288.3 may be a major upstream regulator of the WNT-FOXO1 pathway and activin-SMAD3 pathways previously shown as critical for hESF decidualization. Finally, we explored possible regulators of AC027288.3 expression during human ESF decidualization. Expression was regulated by cAMP and progesterone. Our results suggest that AC027288.3 plays a role in hESF decidualization and identifies several other lncRNA genes that may also play a role. Full article

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14–16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients’ blood. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease marked by abnormal accumulation of extracellular matrix (ECM) due to dysregulated expression of various RNAs in pulmonary fibroblasts. This study utilized RNA-seq data meta-analysis to explore the regulatory network of hub long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in IPF fibroblasts. The meta-analysis unveiled 584 differentially expressed mRNAs (DEmRNA) and 75 differentially expressed lncRNAs (DElncRNA) in lung fibroblasts from IPF. Among these, BCL6, EFNB1, EPHB2, FOXO1, FOXO3, GNAI1, IRF4, PIK3R1, and RXRA were identified as hub mRNAs, while AC008708.1, AC091806.1, AL442071.1, FAM111A-DT, and LINC01989 were designated as hub lncRNAs. Functional characterization revealed involvement in TGF-β, PI3K, FOXO, and MAPK signaling pathways. Additionally, this study identified regulatory interactions between sequences of hub mRNAs and lncRNAs. In summary, the findings suggest that AC008708.1, AC091806.1, FAM111A-DT, LINC01989, and AL442071.1 lncRNAs can regulate BCL6, EFNB1, EPHB2, FOXO1, FOXO3, GNAI1, IRF4, PIK3R1, and RXRA mRNAs in fibroblasts bearing IPF and contribute to fibrosis by modulating crucial signaling pathways such as FoxO signaling, chemical carcinogenesis, longevity regulatory pathways, non-small cell lung cancer, and AMPK signaling pathways. Full article

Hypertrophic cardiomyopathy (HCM) is a disease in which the myocardium of the heart becomes asymmetrically thickened, malformed, disordered, and loses its normal structure and function. Recent studies have demonstrated the significant involvement of inflammatory responses in HCM. However, the precise role of immune-related long non-coding RNAs (lncRNAs) in the pathogenesis of HCM remains unclear. In this study, we performed a comprehensive analysis of immune-related lncRNAs in HCM. First, transcriptomic RNA-Seq data from both HCM patients and healthy individuals (GSE180313) were reanalyzed thoroughly. Key HCM-related modules were identified using weighted gene co-expression network analysis (WGCNA). A screening for immune-related lncRNAs was conducted within the key modules using immune-related mRNA co-expression analysis. Based on lncRNA–mRNA pairs that exhibit shared regulatory microRNAs (miRNAs), we constructed a competing endogenous RNA (ceRNA) network, comprising 9 lncRNAs and 17 mRNAs that were significantly correlated. Among the 26 lncRNA–mRNA pairs, only the MIR210HG–BPIFC pair was verified by another HCM dataset (GSE130036) and the isoprenaline (ISO)-induced HCM cell model. Furthermore, knockdown of MIR210HG increased the regulatory miRNAs and decreased the mRNA expression of BPIFC correspondingly in AC16 cells. Additionally, the analysis of immune cell infiltration indicated that the MIR210HG–BPIFC pair was potentially involved in the infiltration of naïve CD4⁺ T cells and CD8⁺ T cells. Together, our findings indicate that the decreased expression of the lncRNA–mRNA pair MIR210HG–BPIFC was significantly correlated with the pathogenesis of the disease and may be involved in the immune cell infiltration in the mechanism of HCM. Full article

Abnormal sexual maturity exhibits significant detrimental effects on adult health outcomes, and previous studies have indicated that targeting histone acetylation might serve as a potential therapeutic approach to regulate sexual maturity. However, the mechanisms that account for it remain to be further elucidated. Using the mouse model, we showed that Trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, downregulated the protein level of Hdac1 in ovaries to promote the apoptosis of granulosa cells (GCs), and thus arrested follicular development and delayed sexual maturity. Using porcine GCs as a cell model, a novel sexual maturity-associated lncRNA, which was named as the stimulatory factor of follicular development (SFFD), transcribed from mitochondrion and mediated by HDAC1, was identified using RNA sequencing. Mechanistically, HDAC1 knockdown significantly reduced the H3K27ac level at the −953/−661 region of SFFD to epigenetically inhibit its transcription. SFFD knockdown released miR-202-3p to reduce the expression of cyclooxygenase 1 (COX1), an essential rate-limited enzyme involved in prostaglandin synthesis. This reduction inhibited the proliferation and secretion of 17β-estradiol (E2) while promoting the apoptosis of GCs. Consequently, follicular development was arrested and sexual maturity was delayed. Taken together, HDAC1 knockdown-mediated SFFD downregulation promoted the apoptosis of GCs through the miR-202-3p-COX1 axis and lead to delayed sexual maturity. Our findings reveal a novel regulatory network modulated by HDAC1, and HDAC1-mediated SFFD may be a promising new therapeutic target to treat delayed sexual maturity. Full article

Background: Disulfidptosis is a novel form of programmed cell death that unveils promising avenues for the exploration of tumor treatment modalities. Gastric cancer (GC) is a malignant tumor characterized by high incidence and mortality rate. However, there has been no systematic study of disulfidptosis-related long noncoding RNAs (DRLs) signature in GC patients. Methods: The lncRNA expression profiles containing 412 GC samples were acquired from the Cancer Genome Atlas (TCGA) database. Differential expression analysis was performed alongside Pearson correlation analysis to identify DRLs. Prognostically significant DRLs were further screened using univariate COX regression analysis. Subsequently, LASSO regression and multifactorial COX regression analyses were employed to establish a risk signature composed of DRLs that exhibit independent prognostic significance. The predictive value of this risk signature was further validated in a test cohort. The ESTIMATE, CIBERSORT and ssGSEA methodologies were utilized to investigate the tumor immune microenvironment of GC populations with different DRLs profiles. Finally, the correlation between DRLs and various GC drug responses was explored. Results: We established a prognostic signature comprising 12 disulfidptosis-related lncRNAs (AC110491.1, AL355574.1, RHPN1-AS1, AOAH-IT1, AP001065.3, MEF2C-AS1, AC016394.2, LINC00705, LINC01952, PART1, TNFRSF10A-AS1, LINC01537). The Kaplan–Meier survival analysis revealed that patients in the high-risk group exhibited a poor prognosis. Both univariate and multivariate COX regression models demonstrated that the DRLs signature was an independent prognostic indicator in GC patients. Furthermore, the signature exhibited accurate predictions of survival at 1-, 3- and 5- years with the area under the curve (AUC) values of 0.708, 0.689 and 0.854, respectively. In addition, we also observed significant associations between the DRLs signature and various clinical variables, distinct immune landscape and drug sensitivity profiles in GC patients. The low-risk group patients may be more likely to benefit from immunotherapy and chemotherapy. Conclusions: Our study investigated the role and potential clinical implications of DRLs in GC. The risk model constructed by DRLs demonstrated high accuracy in predicting the survival outcomes of GC and improving the treatment efficacy for GC patients. Full article

Long non-coding RNAs (lncRNAs) are crucial modulators in a variety of biological processes, such as gene expression, development, and immune defense. However, little is known about the function of lncRNAs in the development of Asian honey bee (Apis cerana) larval guts. Here, on the basis of our previously obtained deep-sequencing data from the 4-, 5-, and 6-day-old larval guts of A. cerana workers (Ac4, Ac5, and Ac6 groups), an in-depth transcriptome-wide investigation was conducted to decipher the expression pattern, regulatory manners, and potential roles of lncRNAs during the developmental process of A. cerana worker larval guts, followed by the verification of the relative expression of differentially expressed lncRNAs (DElncRNAs) and the targeting relationships within a competing endogenous RNA (ceRNA) axis. In the Ac4 vs. Ac5 and Ac5 vs. Ac6 comparison groups, 527 and 498 DElncRNAs were identified, respectively, which is suggestive of the dynamic expression of lncRNAs during the developmental process of larval guts. A cis-acting analysis showed that 330 and 393 neighboring genes of the aforementioned DElncRNAs were respectively involved in 29 and 32 functional terms, such as cellular processes and metabolic processes; these neighboring genes were also respectively engaged in 246 and 246 pathways such as the Hedgehog signaling pathway and the Wnt signaling pathway. Additionally, it was found that 79 and 76 DElncRNAs as potential antisense lncRNAs may, respectively, interact with 72 and 60 sense-strand mRNAs. An investigation of competing endogenous RNA (ceRNA) networks suggested that 75 (155) DElncRNAs in the Ac4 vs. Ac5 (Ac5 vs. Ac6) comparison group could target 7 (5) DEmiRNAs and further bind to 334 (248) DEmRNAs, which can be annotated to 33 (29) functional terms and 186 (210) pathways, including 12 (16) cellular- and humoral-immune pathways (lysosome pathway, necroptosis, MAPK signaling pathway, etc.) and 11 (10) development-associated signaling pathways (Wnt, Hippo, AMPK, etc.). The RT-qPCR detection of five randomly selected DElncRNAs confirmed the reliability of the used sequencing data. Moreover, the results of a dual-luciferase reporter assay were indicative of the binding relationship between MSTRG.11294.1 and miR-6001-y and between miR-6001-y and ncbi_107992440. These results demonstrate that DElncRNAs are likely to modulate the developmental process of larval guts via the regulation of the source genes’ transcription, interaction with mRNAs, and ceRNA networks. Our findings not only yield new insights into the developmental mechanism underlying A. cerana larval guts, but also provide a candidate ceRNA axis for further functional dissection. Full article

Uterine corpus endometrial carcinoma (UCEC) is the second most common gynecological cancer in the world. With the increased occurrence of UCEC and the stagnation of research in the field, there is a pressing need to identify novel UCEC biomarkers. Disulfidptosis is a novel form of cell death, but its role in UCEC is unclear. We integrate differential analysis and the XGBoost algorithm to determine a disulfidptosis-related characteristic gene (DRCG), namely LRPPRC. By prediction and verification based on online databases, we construct a regulatory network of ceRNA in line with the scientific hypothesis, including a ceRNA regulatory axis and two mRNA-miRNA regulatory axes, i.e., mRNA LRPPRC/miRNA hsa-miR-616-5p/lncRNA TSPEAR-AS2, mRNA LRPPRC/miRNA hsa-miR-4658, and mRNA LRPPRC/miRNA hsa-miR-6783-5p. We use machine learning methods such as GBM to screen out seven disulfidptosis-related characteristic lncRNAs (DRCLs) as predictors, and build a risk prediction model with good prediction ability. SCORE = (1.136*LINC02449) + (−2.173*KIF9-AS1) + $(-$0.235*ACBD3-AS1) + (1.830*AL354892.3) + (−1.314*AC093677.2) + (0.636*AC113361.1) + (−0.589*CDC37L1-DT). The ROC curve shows that in the training set samples, the AUCs for predicting 1-, 3-, 6-, and 10-year OS are 0.804, 0.724, 0.719, and 0.846, respectively. In the test set samples, the AUCs for predicting 1-, 3-, 6-, and 10-year OS are 0.615, 0.657, 0.687, and 0.702, respectively. In all samples, the AUCs for predicting 1-, 3-, 6-, and 10-year OS are 0.752, 0.706, 0.705, and 0.834, respectively. CP724714 has been screened as a potential therapy option for individuals who have a high risk of developing UCEC. Two subtypes of disulfidptosis-related genes (DRGs) and two subtypes of DRCLs are obtained by NMF method. We find that subtype N1 of DRGs is mainly enriched in various metabolic pathways, and subtype N1 may play a significant role in the process of disulfidptosis. Our study confirms for the first time that disulfidptosis plays a role in UCEC. Our findings help improve the prognosis and treatment of UCEC. Full article

Long noncoding RNAs (lncRNAs) are transcripts with lengths of more than 200 nt and limited protein-coding potential. They were found to play important roles in plant stress responses. In this study, the maize drought-tolerant inbred line AC7643 and drought-sensitive inbred line AC7729/TZSRW, as well as their recombinant inbred lines (RILs) were selected to identify drought-responsive lncRNAs in roots. Compared with non-responsive lncRNAs, drought-responsive lncRNAs had different sequence characteristics in length of genes and number of exons. The ratio of down-regulated lncRNAs induced by drought was significantly higher than that of coding genes; and lncRNAs were more widespread expressed in recombination sites in the RILs. Additionally, by integration of the modifications of DNA 5-methylcytidine (5mC), histones, and RNA N6-methyladenosine (m⁶A), it was found that the enrichment of histone modifications associated with transcriptional activation in the genes generated lncRNAs was lower that coding genes. The lncRNAs-mRNAs co-expression network, containing 15,340 coding genes and 953 lncRNAs, was constructed to investigate the molecular functions of lncRNAs. There are 13 modules found to be associated with survival rate under drought. We found nine SNPs located in lncRNAs among the modules associated with plant survival under drought. In conclusion, we revealed the characteristics of lncRNAs responding to drought in maize roots based on multiomics studies. These findings enrich our understanding of lncRNAs under drought and shed light on the complex regulatory networks that are orchestrated by the noncoding RNAs in response to drought stress. Full article