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At least 19 recordsLinked to original sources

PubMed2025

Global lncRNA expression profiles in medulloblastoma reveal crucial lncRNA-oncogene interactions in Sonic hedgehog and Group 4.

BACKGROUND: Advances in multi-omic studies have improved medulloblastoma (MB) characterization, yet novel molecular biomarkers are needed to refine tumor biology and therapeutic strategies. Current profiling mainly targets the protein-coding genome, while the potential of noncoding regions remains unexplored. This study aims to identify long noncoding RNAs (lncRNAs), emerging as crucial regulators in MB, as potential key biomarkers specific to molecular group, enhancing understanding of MB's genomic landscape. METHODS: RNA-seq data from 54 Spanish MB patients (C1) and 207 public samples (C2) were analyzed to profile lncRNAs. Expression and Weighted Gene Coexpression Network (WGCNA) analyses were performed to identify lncRNA-oncogene interactions. Group-specific interactions were examined to infer their role in MB pathogenesis and highlight potential lncRNA involvement in disease mechanisms. RESULTS: LncRNA expression profiles identified 4 clusters corresponding to the MB molecular groups, confirming their potential as biomarkers. Expression and WGCNA analyses revealed group-specific lncRNAs for Sonic hedgehog (SHH), Group 3 (Gr3), and Group 4 (Gr4) MB. Lnc-SMARCA2 was exclusively upregulated in SHH MB, and associated with ATOH1 and PDLIM3, key cilium regulators of this group's cell of origin. In Gr4 MB, MGC32805 and LOC107986446 were upregulated and linked to SNCAIP, potentially influencing PRDM6 activation via enhancer hijacking. Additionally, a 5-lncRNA signature linked to phototransduction was exclusive to Gr3, offering insights into its lineage switch and molecular regulation. CONCLUSIONS: Lnc-SMARCA2 and, MGC32805 and LOC107986446, are exclusively deregulated in SHH and Gr4 MB, respectively, and directly associated with group-specific MB oncogenes, representing promising novel biomarkers and therapeutic targets in MB.

cancer biomarkers↗

PubMed2026

METTL14 alleviates pyroptosis of placental trophoblasts in gestational diabetes mellitus through the lncRNA MEG8/WNT7A axis via m6A modification.

Gestational diabetes mellitus (GDM) is a pregnancy complication associated with abnormal placental trophoblast function. Pyroptosis has been implicated in GDM pathogenesis, yet the role of m6A modification in this process remains unclear. We hypothesized that METTL14 regulates trophoblast pyroptosis through m6A-dependent modulation of the lncRNA MEG8/WNT7A axis. This study investigated the mechanism of METTL14 in pyroptosis of placental trophoblasts in GDM. HG-treated HTR8/SVneo cells were used as a cell model. METTL14, WNT7A, and lncRNA MEG8 expression was detected by RT-qPCR and western blot. Placental damage, cell injury, and pyroptosis markers were assessed. YTHDF2-mediated m6A enrichment on lncRNA MEG8, the interaction between lncRNA MEG8 and EZH2, and H3K27me3 enrichment on the WNT7A promoter were analyzed. Results showed that lncRNA MEG8 was upregulated, while METTL14 and WNT7A were downregulated. METTL14 overexpression reduced placental damage and trophoblast pyroptosis. Mechanistically, METTL14 suppressed lncRNA MEG8 expression through YTHDF2-mediated m6A methylation. Reduced lncRNA MEG8 decreased EZH2 recruitment to the WNT7A promoter, lowered H3K27me3 levels, and consequently promoted WNT7A expression. Rescue experiments confirmed that lncRNA MEG8 overexpression or WNT7A knockdown attenuated the suppressive effect of METTL14 on pyroptosis. In conclusion, METTL14 acts as an upstream regulator that inhibits trophoblast pyroptosis and ameliorates GDM-induced damage through the lncRNA MEG8/WNT7A axis via YTHDF2-mediated m6A modification, highlighting METTL14 as a potential therapeutic target.

Humans↗

PubMed2026

A novel deep learning-driven framework for improving lncRNA comprehensive annotation with LncADeep 2.0.

MOTIVATION: Long non-coding RNAs (lncRNAs) have emerged as crucial players in diverse physiological and pathological processes, yet the biological mechanisms of the vast majority of lncRNAs remain elusive. To fill this gap, it is necessary to improve the accuracy of lncRNA identification and functional annotation. RESULTS: Here, we introduce LncADeep 2.0, an integrated deep learning framework designed to meet these needs. In the identification module, LncADeep 2.0 incorporated novel peptide features along with sequence and structural information, demonstrating superior performance over our previous LncADeep and other existing tools on both annotated transcripts from GENCODE and RNA-seq data. For functional annotation, LncADeep 2.0 leveraged lncRNA-centric interaction networks and gene ontology terms through the transfer learning strategy to achieve robust annotation performance with limited functional data. Compared to LncADeep, LncADeep 2.0 could accurately elucidate the general functions of given lncRNA sequences, predict tissue- or cell-type-specific functions from bulk and single-cell RNA-seq data, and establish connections between tumor-associated lncRNAs and genomic markers. Overall, LncADeep 2.0 stands out as an efficient and reliable tool for lncRNA identification and functional annotation across a wide spectrum of biological processes. AVAILABILITY AND IMPLEMENTATION: LncADeep 2.0 is available for use at https://github.com/Jefferson-Chou/LncADeep2 and https://doi.org/10.5281/zenodo.17164767.

RNA, Long Noncoding↗

PubMed2026

LncRNA HAR1A in triple-negative breast cancer: mechanisms and the role of polymorphism rs 6089838 in susceptibility.

BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly recognized as crucial regulators and potential biomarkers in triple-negative breast cancer (TNBC). This study examined the link between the rs6089838 polymorphism in HAR1A and TNBC susceptibility/progression and function. RESEARCH DESIGN AND METHODS: 197 TNBC patients and 185 healthy controls were recruited. Rs6089838 genotyping and serum lncRNA HAR1A quantification were performed using qRT PCR. Survival was analyzed via KM and Cox regression.. Cellular proliferation, migration, and invasion were measured using CCK-8 and Transwell assays. RESULTS: The GG genotype significantly lowered TNBC risk versus the AA genotype (OR =0.393, p = 0.002). GA/GG genotypes were associated with more favorable clinicopathological features. Serum lncRNA HAR1A was downregulated in TNBC patients (p < 0.001) and was positively correlated with the protective G allele frequency (p < 0.001). GA/GG carriers showed significantly longer overall survival than AA homozygotes (p < 0.001). Functional studies confirmed that HAR1A overexpression via pcDNA3.1 suppressed proliferation, migration, and invasion in breast cancer cell lines. Conversely, siRNA-mediated lncRNA HAR1A knockdown enhanced these oncogenic traits. CONCLUSION: The G allele of HAR1A rs6089838 represents a protective variant against TNBC susceptibility and progression, likely through HAR1A's tumor-suppressive activity. This SNP may have potential as a biomarker for TNBC risk and prognosis assessment.

Humans↗

PubMed2024

Construction of an immunogenic cell death-related LncRNA signature to predict the prognosis of patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common malignant diseases worldwide. This study aimed to construct an immunogenic cell death (ICD)-related long non-coding RNA (lncRNA) signature to effectively predict the prognosis of LUAD. METHODS: The RNA-sequencing and clinical data of LUAD were downloaded from The Cancer Genome Atlas (TCGA). Least absolute shrinkage and selection operator (LASSO) and stepwise multivariate Cox proportional hazard regression analysis were utilized to construct lncRNA signature. Then, the reliability of the signature was evaluated in the training, validation and whole cohorts. The differences in the immune landscape and drug sensitivity between the low- and high-risk groups were analyzed. Finally, the expression level of the selected ICD-related lncRNAs in LUAD cell lines via reverse transcription quantitative PCR (RT-qPCR). CCK-8 and transwell assays were performed to study biological function of AC245014.3. RESULTS: A signature consisting of 5 ICD-related lncRNAs was constructed. Kaplan Meier (K-M) survival analysis showed shorter overall survival (OS) in high-risk group. The receiver operating characteristic (ROC) curves and Multivariate Cox regression analysis showed the signature was good predictive and independent prognostic factor in LUAD. Moreover, the high-risk group had a lower level of antitumor immunity and was less sensitive to some chemotherapeutics and targeted drugs. Finally, the expression level of selected ICD-related lncRNAs was validated in LUAD cell lines by RT-qPCR. Knockdown of AC245014.3 significantly suppressed LUAD proliferation, migration and invasion. CONCLUSIONS: In this study, an ICD-related lncRNA signature was constructed, which could accurately predict the prognosis of LUAD patients and guide clinical treatment.

Humans↗

PubMed2025

LncRNA Profiling and ceRNA Network Construction of Intrauterine Exosomes in Goats During Embryo Implantation.

Exosomes have been shown to play an important role in embryo implantation, but the mechanism is still unclear. This study aimed to investigate the functional roles of lncRNAs in intrauterine exosomes in goat pregnancy. We used RNA-seq to identify the lncRNA profiles of exosomes obtained from goat uterine rinsing fluid at 5, 15, and 18 days of gestation. In addition, we performed weighted gene co-expression network analysis based on differentially expressed mRNAs (DEMs) and lncRNAs (DELs). Functional enrichment analyses of gene modules were conducted using Gene Ontology classification (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. A lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) regulatory network was constructed based on predictive interaction derived from miRTarBase, miRDB and RNAhybrid databases. Altogether, 831 DELs were identified. GO and KEGG analysis showed that the target genes were enriched in processes associated with embryo implantation, such as signaling receptor activity, binding and immune response. Nine functional co-expression modules were enriched in various biological processes, such as metabolic pathways, protein transport, cell cycle and VEGF signaling pathway. Additionally, 12 lncRNA-mediated ceRNA networks were constructed. Our results demonstrate that exosomal lncRNAs in uterine flushing fluid exhibit dynamic changes across gestational stages and play an important role in regulating the uterine microenvironment during embryo implantation. These findings provide a foundational basis for screening exosome-derived lncRNAs that influence embryo implantation and contribute to elucidating the mechanistic roles of lncRNAs in exosome-mediated processes during early pregnancy.

embryo implantation↗

PubMed2026

A Combination of Alleles in LMOD2 and a lncRNA is Strongly Associated With Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels.

A previous genome-wide association study identified regions on canine chromosome (cfa) 13 and 14 associated with early onset myxomatous mitral valve disease (MMVD) in Cavalier King Charles Spaniels (CKCS). In the present study, whole genome sequencing (WGS) of 9 CKCS cases (mitral regurgitation (MR) before 4.5 years or congestive heart failure (CHF) at any age due to MMVD) and 10 CKCS controls (no or mild MR after 8 years of age) identified > 2000 genetic variants in the MMVD associated cfa13 and cfa14 regions. Ensembl Variant Effect Predictor (VEP) identified a possible functional impact of 18 variants. These were genotyped in 250 CKCS; 117 cases and 133 controls. The most significantly associated variants were a splice-site variant in a long noncoding RNA (lncRNA) on cfa13, a nonsynonymous variant in HYAL4, a 39 base-pair insertion in LMOD2 and a synonymous variant in ENSCAFG00000024436 (p-values from 2.03E-08 to 4.20E-06). Concomitant homozygosity for risk alleles in LMOD2 and the lncRNA gave an odds-ratio for MMVD of 52.5 compared to homozygosity for the nonrisk alleles (p = 0.00034, 95% CI: 8.8-1023.8). Upon validation of our results in an independent cohort, this gene variant combination in CKCS is expected to enable targeted breeding programs to reduce MMVD prevalence in CKCS.

Animals↗

PubMed2026

LncRNA RP11-708J19.2 promotes colorectal cancer progression by binding to SIRT7 via regulating H3K18ac.

Colorectal cancer (CRC) is a prevalent malignancy with a complex genetic basis. Recent genome-wide association studies (GWAS) have identified a susceptibility locus at 3p21.31, however, the functional SNP(s) underlying the association between the 3p21.31 region and CRC remain to be elucidated. In this study, we identified rs2101247 as the potential functional SNP and further demonstrated that rs2101247 is significantly associated with the expression of the nearby long non-coding RNA (lncRNA) RP11-708J19.2 (ENSG00000271161.1). Functional experiments showed that RP11-708J19.2 is upregulated in CRC tumor tissues, and its knockdown reduces cell viability while promoting apoptosis in SW1116 and HCT116 cell lines. Mechanistically, RP11-708J19.2 interacts directly with the deacetylase SIRT7, modulating histone H3K18 acetylation (H3K18ac). Specifically, RP11-708J19.2 knockdown leads to a significant upregulation of H3K18ac levels, implicating a SIRT7-mediated epigenetic pathway in CRC progression. Our findings elucidate a novel functional SNP-lncRNA axis that contributes to CRC pathogenesis, providing potential biomarkers for early detection and therapeutic targets for intervention.

Humans↗

PubMed2026

An inflammatory bowel disease-linked lncRNA suppresses transcription factor T-BET expression in T cells to limit intestinal inflammation.

Among the tens of thousands of annotated long noncoding RNAs (lncRNAs) in the human genome, only a small fraction have been functionally characterized. Here, we show that a well-established inflammatory bowel disease (IBD) risk locus encoded a conserved lncRNA, lnc15 (2310015A10Rik/ENSMUSG00000097729), whose structure was destabilized by risk-associated variants, leading to its degradation. Deletion of lnc15 in mice resulted in molecular features of inflammation under steady-state conditions and conferred heightened susceptibility to experimental colitis. Lnc15 was abundantly expressed in T cells, with highest expression in regulatory T (Treg) cells. Mechanistically, lnc15 suppressed the transcription factor T-BET by recruiting the CCR4-NOT RNA degradation complex to Tbx21 mRNA. Our study identifies that lnc15 simultaneously enhances Treg cell suppressive function and impairs conventional T cell pathogenicity in the context of intestinal inflammation. Collectively, these findings identify lnc15 as a functional lncRNA that links noncoding genetic variation to immune regulation and prevention of mucosal inflammation. VIDEO ABSTRACT.

RNA, Long Noncoding↗

PubMed2026

A Proteogenomic Approach to Discover Novel lncRNA-Derived Microproteins and Their Potential Clinical Utility in Hepatocellular Carcinoma.

Microproteins (i.e., peptides) are increasingly recognized for their functions in versatile biological contexts, but their clinical relevance and utility remain largely unexplored. Proteogenomic approaches can accelerate microprotein discovery in clinical samples by integrating proteomic data with genomics and transcriptomics evidence. However, long noncoding RNA (lncRNA)-derived microproteins (lncPeps) remain largely unidentified, resulting in unmatchable MS/MS spectra. To solve this problem, we have used high-quality Ribo-seq translatomic datasets to generate an extensive database of human liver lncRNA-derived open reading frames (lncORFs), which we subsequently applied to proteomics data of tumor-adjacent normal tissue pairs from hepatocellular carcinoma (HCC) patients. Using the new database, we discovered 104 novel lncPeps, including 46 lncPeps differentially expressed between tumor and nontumor tissues, and 13 lncPeps with significant correlation with prognosis. Remarkably, combining the expression of lncPeps with canonical proteins in a LASSO regression model improved predictive performance for recurrence, increasing the AUC by 0.005 to 0.085 across three recurrence time points. These findings suggest that the discovery of lncPeps contributes to our understanding of the molecular heterogeneity and progression of HCC and broadens the range of potential biomarker candidates and treatment targets for the disease.

Humans↗

PubMed2025

The involvement of lncRNA EMSLR in the disulfidptosis and progression of endometrial carcinoma.

The incidence of endometrial cancer (EC) continues to rise. Disulfidptosis, a novel form of cell death, may represent a potential therapeutic target in EC. Through bioinformatic analysis of The Cancer Genome Atlas (TCGA) database, E2F1 mRNA-stabilizing lncRNA (EMSLR) was identified as a lncRNA related to disulfidptosis in EC. Functional assays, including cell proliferation and xenograft assays, demonstrated that knockdown of EMSLR significantly impeded EC cell proliferation, whereas overexpression of EMSLR promoted cell viability. Additionally, EMSLR was found to be associated with glucose uptake and NADPH production in glucose-restricted culture conditions. Moreover, downregulation of EMSLR markedly increased cell death and induced cytoskeletal collapse under glucose deprivation, as evidenced by F-actin and cell death staining. Notably, we observed a strong correlation between EMSLR and the c-MYC-GLUT1 pathway. Mechanistically, EMSLR was found to mediate the expression and nuclear translocation of c-MYC, thereby regulating the progression of EC and its associated disulfidptosis. In conclusion, EMSLR is identified as a disulfidptosis-related gene in endometrial cancer. Elucidating the function and molecular mechanisms of EMSLR in EC presents a promising avenue for therapeutic intervention in patients.

Female↗

PubMed2024

CRISPRi screens identify the lncRNA, LOUP, as a multifunctional locus regulating macrophage differentiation and inflammatory signaling.

Long noncoding RNAs (lncRNAs) account for the largest portion of RNA from the transcriptome, yet most of their functions remain unknown. Here, we performed two independent high-throughput CRISPRi screens to understand the role of lncRNAs in monocyte function and differentiation. The first was a reporter-based screen to identify lncRNAs that regulate TLR4-NFkB signaling in human monocytes and the second screen identified lncRNAs involved in monocyte to macrophage differentiation. We successfully identified numerous noncoding and protein-coding genes that can positively or negatively regulate inflammation and differentiation. To understand the functional roles of lncRNAs in both processes, we chose to further study the lncRNA LOUP [lncRNA originating from upstream regulatory element of SPI1 (also known as PU.1)], as it emerged as a top hit in both screens. Not only does LOUP regulate its neighboring gene, the myeloid fate-determining factor SPI1, thereby affecting monocyte to macrophage differentiation, but knockdown of LOUP leads to a broad upregulation of NFkB-targeted genes at baseline and upon TLR4-NFkB activation. LOUP also harbors three small open reading frames capable of being translated and are responsible for LOUP's ability to negatively regulate TLR4/NFkB signaling. This work emphasizes the value of high-throughput screening to rapidly identify functional lncRNAs in the innate immune system.

RNA, Long Noncoding↗

PubMed2026

Differentiation-independent activation of HPV genome replication by the lncRNA DINO.

Human papillomaviruses (HPVs) rely on multiple host cell factors to replicate the viral genome, yet the contribution of host long non-coding RNAs (lncRNAs) to viral genome maintenance and amplification in the productive life cycle remains poorly understood. In this study, we show that the lncRNA damage-induced long non-coding RNA (DINO) is a driver of HPV DNA replication. DINO levels increase during keratinocyte differentiation, and ectopic expression of DINO promotes both HPV genome replication and the formation of replication foci, and this is independent of keratinocyte differentiation signals. Ectopic DINO expression increases select early viral transcript levels, including E1^E4, E1, and E2. Notably, DINO's subcellular localization is also context-dependent: during DNA damage, DINO is predominantly cytoplasmic, but during keratinocyte differentiation, nuclear retention is observed. This differential localization suggests that DINO has distinct functional roles in keratinocyte differentiation and HPV biology. Our findings highlight DINO as a lncRNA that promotes HPV genome replication and suggest that lncRNAs may play underappreciated roles in host-virus interactions. This work provides a foundation for further exploration of lncRNAs as potential therapeutic targets in HPV-associated diseases.IMPORTANCEHuman papillomaviruses (HPVs) are the causative agents of many anogenital tract and oral cancers, yet the host factors that trigger and support viral genome replication during the productive life cycle are incompletely understood. This study identifies the long non-coding RNA DINO as a host regulator that promotes HPV DNA replication, replication focus formation, and early viral gene expression independently of keratinocyte differentiation. We further show that DINO exhibits context-dependent subcellular localization, suggesting distinct functional roles in cellular stress responses and HPV biology. These findings reveal an underappreciated role for host lncRNAs in virus-host interactions and provide new insight into cellular pathways that support HPV genome replication.

Virus Replication↗

PubMed2026

Integrative Pan-Cancer Characterization of lncRNA UPK1A-AS1 and Its Role in Hypoxia-Associated Sorafenib Resistance in Hepatocellular Carcinoma.

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of tumor initiation and progression through transcriptional and posttranscriptional mechanisms. UPK1A antisense RNA 1 (UPK1A-AS1), a cancer-associated lncRNA, has been reported to participate in oncogenic processes; however, its overall landscape across human malignancies and its biological role in therapy resistance remain poorly understood. Given the increasing importance of identifying functional lncRNAs with prognostic and therapeutic potential, this study presents a comprehensive multiomics characterization of UPK1A-AS1 and its experimental validation in hepatocellular carcinoma (HCC). We integrated datasets from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), the cancer immunology data engine (CIDE), and the cBioPortal for cancer genomics (cBioPortal) to systematically assess its expression pattern, genomic alterations, clinical significance, and immunological associations. Our analyses revealed that UPK1A-AS1 is significantly upregulated in multiple tumor types, with copy-number amplification as the predominant genomic alteration driving its overexpression. Elevated UPK1A-AS1 expression was correlated with advanced disease stage, poor differentiation, immune exclusion, and unfavorable prognosis, supporting its potential as a cancer type-dependent biomarker. In parallel, functional studies demonstrated that hypoxia transcriptionally induces UPK1A-AS1 in HCC, where it promotes sorafenib resistance by suppressing apoptosis. Silencing UPK1A-AS1 restored apoptotic and enhanced sorafenib efficacy both in vitro and in vivo. Collectively, our findings suggest that UPK1A-AS1 is a hypoxia-inducible oncogenic lncRNA that plays dual roles in cancer, with cancer type-dependent associations with progression and immune modulation across malignancies and mechanistically mediating hypoxia-associated drug resistance in HCC.

Humans↗

PubMed2026

Identification of a necroptosis-related lncRNA prognostic signature and the hub RBP HNRNPK in esophageal squamous cell carcinoma.

ObjectiveEsophageal squamous cell carcinoma (ESCC) is a malignant tumor with poor prognosis. Necroptosis is important for tumor immunity, but its role in ESCC remains unclear. This retrospective bioinformatics study aimed to investigate the prognostic value of necroptosis-related long non-coding RNAs (lncRNAs) and to identify key lncRNA-binding proteins (RBPs) in ESCC patients.MethodsRNA transcriptome and clinical data of ESCC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Necroptosis-related lncRNAs were identified through correlation analysis with necroptosis-related genes, subjected to consensus cluster analysis, and used to construct a prognostic risk model via least absolute shrinkage and selection operator (LASSO) regression. The hub RBP was experimentally validated by quantitative polymerase chain reaction (qPCR) using 30 pairs of ESCC and adjacent normal tissues from patients who underwent surgical resection.ResultsA total of 30 necroptosis-related lncRNAs were significantly correlated with overall survival (OS). The upregulated lncRNAs in the risk model were associated with high immune scores, innate immune cell infiltration, cluster 2 classification, and advanced T-stage disease (p < 0.05). Three hub RBPs (HNRNPA1, HNRNPC, and HNRNPK) were identified through protein-protein interaction network analysis. qPCR confirmed that HNRNPK was significantly overexpressed in ESCC tissues compared to adjacent normal tissues (p < 0.05).ConclusionsThe necroptosis-related lncRNA risk model is an independent prognostic factor for ESCC patients. HNRNPK was identified as a hub RBP significantly overexpressed in ESCC tissues. We hypothesize that HNRNPK may promote tumor progression through regulating proto-oncogene expression or modulating the immune microenvironment, though this requires further mechanistic validation.

Humans↗

PubMed2024

Expression profile of long noncoding RNAs and comprehensive analysis of lncRNA-cisTF-DGE regulation in condyloma acuminatum.

OBJECTIVE: To identify differentially expressed long noncoding RNAs (lncRNAs) in condyloma acuminatum (CA) and to explore their probable regulatory mechanisms by establishing coexpression networks. METHODS: High-throughput RNA sequencing was performed to assess genome-wide lncRNA expression in CA and paired adjacent mucosal tissue. The expression of candidate lncRNAs and their target genes in larger CA specimens was validated using real-time quantitative reverse transcriptase polymerase chain reaction (RT‒qPCR). Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for the functional enrichment analysis of these candidate lncRNAs and differential mRNAs. The coexpressed mRNAs of the candidate lncRNAs, calculated by Pearson's correlation coefficient, were also analysed using GO and KEGG analysis. In addition, the interactions among differentially expressed lncRNAs (DElncRNAs)-cis-regulatory transcription factors (cisTFs)-differentially expressed genes (DEGs) were analysed and their network was constructed. RESULTS: A total of 546 lncRNAs and 2553 mRNAs were found to be differentially expressed in CA compared to the paired control. Functional enrichment analysis revealed that the DEGs coexpressed with DElncRNAs were enriched in the terms of cell adhesion and keratinocyte differentiation, and the pathways of ECM-receptor interaction, local adhesion, PI3K/AKT and TGF-ß signaling. We further constructed the network among DElncRNAs-cisTFs-DEGs and found that these 95 DEGs were mainly enriched in GO terms of epithelial development, regulation of transcription or gene expression. Furthermore, the expression of 3 pairs of DElncRNAs and cisTFs, EVX1-AS and HOXA13, HOXA11-AS and EVX1, and DLX6-AS and DLX5, was validated with a larger number of specimens using RT‒qPCR. CONCLUSION: CA has a specific lncRNA profile, and the differentially expressed lncRNAs play regulatory roles in mRNA expression through cis-acting TFs, which provides insight into their regulatory networks. It will be useful to understand the pathogenesis of CA to provide new directions for the prevention, clinical treatment and efficacy evaluation of CA.

RNA, Long Noncoding↗

PubMed2026

Differentiation-independent Activation of HPV Genome Replication by the lncRNA DINO.

Human papillomaviruses (HPV) rely on multiple host cell factors to replicate the viral genome, yet the contribution of host long noncoding RNAs (lncRNAs) to viral genome maintenance and amplification in the productive life cycle remains poorly understood. In this study, we show that the lncRNA DINO is a driver of HPV DNA replication. DINO levels increase during keratinocyte differentiation and ectopic expression of DINO promotes both HPV genome replication and the formation of replication foci, and this is independent of keratinocyte differentiation signals. Ectopic DINO expression increases select early viral transcript levels including E1^4, E1, and E2. Notably, DINO's subcellular localization is also context-dependent: during DNA damage DINO is predominantly cytoplasmic, but during keratinocyte differentiation nuclear retention is observed. This differential localization suggests that DINO has distinct functional roles in keratinocyte differentiation and HPV biology. Our findings highlight DINO as a lncRNA that promotes HPV genome replication and suggest that lncRNAs may play underappreciated roles in host-virus interactions. This work provides a foundation for further exploration of lncRNAs as potential therapeutic targets in HPV-associated diseases.

Journal Article↗

PubMed2026

CONCR lncRNA organizes a 3'-end structural domain that engages DDX11 for DNA replication and sister chromatid cohesion.

CONCR (DDX11-AS1) is a long noncoding RNA (lncRNA) necessary for the establishment of sister chromatid cohesion. Despite its activity, whether it contains structural elements essential for its function remains unknown. We determined CONCR structural organization and its functional relevance by integrating selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP), atomic force microscopy (AFM), evolutionary analyses, cryo-electron microscopy (cryo-EM), and cellular genetic studies. We found that CONCR molecular topology is modular, with highly structured domains connected by flexible linkers. A large 3'-end domain is responsible for binding to DDX11 helicase, can trigger DDX11 ATPase activity, and is essential for proper DNA replication and sister chromatid cohesion. This 3' end comprises two helical arms connecting two multiway junctions with structural motifs conserved among all primate groups and required for DDX11 binding and sister chromatid cohesion. Our results highlight the critical role of RNA structure in CONCR function, with a highly structured 3'-end domain acting as a loading and activation platform for DDX11 helicase.

DEAD-box RNA Helicases↗