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PubMed2003

Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlk1-Gtl2 imprinted cluster on mouse chromosome 12.

Genomic imprinting causes parental origin-specific gene expression. Cis-acting regulatory elements that control imprinting are not fully understood but involve regions that become differentially methylated on the two parental chromosomes during male and female gametogenesis. Understanding properties of maternally and paternally inherited imprints provides insight into the mechanisms and evolution of genomic imprinting. Previously we identified an intergenic germline-derived differentially methylated region (IG-DMR) that is a candidate control element for an imprinted domain on distal mouse chromosome 12 (ref. 5). The 1-Mb cluster contains the paternally expressed protein-coding genes Dlk1 (refs. 6,7) and Dio3 (ref. 8,9) and several maternally expressed non-coding RNAs, including Gtl2 (refs. 6,7,10) and C/D snoRNAs. A retrotransposon-like gene (Rtl1) is expressed from the paternal chromosome and has an antisense transcript expressed from the maternal chromosome containing two microRNAs with full complementarity to Rtl1 (ref. 12). Here we show that deletion of the IG-DMR from the maternally inherited chromosome causes bidirectional loss of imprinting of all genes in the cluster. When the deletion is transmitted from the father, imprinting is unaltered. These results prove that the IG-DMR is a control element for all imprinted genes on the maternal chromosome only and indicate that the two parental chromosomes control allele-specific gene expression differently.

Animals↗

PubMed2002

Effect of TSIX disruption on XIST expression in male ES cells.

XIST and its antisense partner, TSIX, encode non-coding RNAs and play key roles in X chromosome inactivation. Targeted disruption of TSIX causes ectopic expression of XIST in the extraembryonic tissues upon maternal transmission, which subsequently results in embryonic lethality due to inactivation of both X chromosomes in females and a single X chromosome in males. TSIX, therefore, plays a crucial role in maintaining the silenced state of XIST in CIS and regulates the imprinted X inactivation in the extraembryonic tissues. In this study, we examined the effect of TSIX disruption on XIST expression in the embryonic lineage using embryonic stem (ES) cells as a model system. Upon differentiation, XIST is ectopically activated in a subset of the nuclei of male ES cells harboring the TSIX-deficient X chromosome. Such ectopic expression, however, eventually ceased during prolonged culture. It is likely that surveillance by the X chromosome counting mechanism somehow shuts off the ectopic expression of XIST before inactivation of the X chromosome.

Animals↗

PubMed2026

Contrasting regulation of protein-coding genes and lncRNA homeologs in allotetraploid Coffea arabica.

A chromosome-level Bourbon assembly revealed that protein-coding homeologs are predominantly co-regulated between subgenomes. In contrast, intergenic lncRNAs display a modest, but statistically consistent bias toward subgenome E across diverse developmental and stress contexts. Coffea arabica is an allotetraploid species derived from natural hybridization between C. canephora and C. eugenioides, which contributed the C and E subgenomes, respectively. This genomic origin poses major challenges for genome assembly, annotation, and the interpretation of gene regulation. In this study, a high-quality genome assembly of C. arabica was generated and annotated, with particular emphasis on identifying protein-coding genes and intergenic long non-coding RNAs (lincRNAs). Homeologous relationships between genes from the C and E subgenomes were established, providing a robust framework to investigate subgenomic conservation and regulatory divergence. Using an extensive collection of publicly available RNA-seq libraries spanning multiple developmental stages, tissues, and environmental conditions, the relative transcriptional contribution of each subgenome was evaluated. On a global scale, gene expression was largely balanced between subgenomes, with no consistent evidence of subgenome dominance. While protein-coding genes showed comparable regulatory behavior across subgenomes, lincRNAs exhibited a more asymmetric expression pattern, suggesting higher subgenome-specific expression that is interpreted here as a consistent directional tendency rather than as evidence of subgenome dominance. Together, these results provide new insights into the regulatory architecture of the C. arabica genome and establish a foundational genomic and transcriptomic resource for future functional studies and crop improvement efforts.

Coffea↗

PubMed2025

Genome-Wide Mining of lncRNAs Reveals Their Potential Regulatory Role in the Evolution of Viviparity.

Reproduction in vertebrates usually involves egg-laying (oviparity) or live-bearing (viviparity). Oviparity is the ancestral trait from which viviparity has independently evolved more than 100 times in squamate reptiles. This transition involves a series of physiological and structural changes, including the degeneration of eggshell and the evolution of a placenta and differences in the temporal and spatial expression patterns of some functional genes that drive the structural transformation. Long non-coding RNAs (lncRNAs) play important roles in the regulation of gene expression, yet it remains unclear whether they participate in gene expression shifts during the transition from oviparity to viviparity, and if so how. Therefore, we employ deep mining to identify novel lncRNAs of a closely related oviparous-viviparous pair of lizards (Phrynocephalus przewalskii and P. vlangalii). We construct cis- and trans-regulatory networks between lncRNAs and target genes using the transcriptomic data of oviduct or uteri tissues across reproductive periods. Results show that lncRNAs that regulate eggshell gland developmental genes in the oviparous lizard are lost or less expressed in the viviparous lizard. A number of lncRNAs involved in the regulation of placental development and embryo attachment in viviparous species have no orthologs in oviparous species, and others show little or no expression. Accordingly, lncRNAs may play important regulatory roles in the physiological and structural changes in the transition from oviparity to viviparity. These results open doors to the further elucidation of genetic regulatory networks.

Animals↗

PubMed2026

Transcriptome changes in circulating immune cells of critical COVID-19 patients predict a specific metabolic and epigenetic imprint.

BACKGROUND: The progression to critical COVID-19 arises predominantly from a dysregulated host immune response although the underlying regulatory mechanisms still remain partially elusive. This limits a prompt prediction of the disease progression, reduces the therapeutic options and restrains our understanding of “long COVID”. METHODS: Here, we analyzed the transcriptome of peripheral blood mononuclear cells (PBMCs) collected from COVID-19 patients experiencing different degrees of the disease (mild and critical), and control patients enrolled in the clinical trial COntAGIouS as well as independent bulk RNA-seq, single-cell RNA-seq and proteomic datasets. RESULTS: In critical COVID-19 patients, the integrative analysis of transcriptomic data revealed an altered regulatory network involving microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and coding genes that control mRNA translation-related genes, epigenetics, and metabolism. In parallel, we observed an upregulation of tRNA aminoacylation genes in critical COVID-19 patients by the analysis of either bulk or single-cell RNA-seq data from publicly available independent cohorts. Additionally, we found increased expression of coding genes enriched for the cognate amino acids (glycine, alanine, isoleucine and tyrosine), all related to protein localization, post-translational modifications, and cell metabolism in our cohort. Similar alterations in amino acid frequency were found in an independent proteomic dataset. CONCLUSIONS: Collectively, our findings indicate a broad perturbation of the gene expression landscape that characterizes the aberrant host immune response in critical COVID-19 patients and is potentially coordinated by miRNA and tRNA metabolism alterations. TRIAL REGISTRATION: COntAGIouS, NCT04327570. Registered 26 March 2020, https://clinicaltrials.gov/ct2/show/NCT04327570 .

Female↗

PubMed1998

Activity-dependent regulation of dendritic BC1 RNA in hippocampal neurons in culture.

Several neuronal RNAs have been identified in dendrites, and it has been suggested that the dendritic location of these RNAs may be relevant to the spatiotemporal regulation of mosaic postsynaptic protein repertoires through transsynaptic activity. Such regulation would require that dendritic RNAs themselves, or at least some of them, be subject to physiological control. We have therefore examined the functional regulation of somatodendritic expression levels of dendritic BC1 RNA in hippocampal neurons in culture. BC1 RNA, an RNA polymerase III transcript that is a component of a ribonucleoprotein particle, became first detectable in somatodendritic domains of developing hippocampal neurons at times of initial synapse formation. BC1 RNA was identified only in such neurons that had established synapses on cell bodies and/or developing dendritic arbors. When synaptic contact formation was initiated later in low-density cultures, BC1 expression was coordinately delayed. Inhibition of neuronal activity in hippocampal neurons resulted in a substantial but reversible reduction of somatodendritic BC1 expression. We conclude that expression of BC1 RNA in somatic and dendritic domains of hippocampal neurons is regulated in development, and is dependent upon neuronal activity. These results establish (for the first time to our knowledge) that an RNA polymerase III transcript can be subject to control through physiological activity in nerve cells.

Animals↗

PubMed2024

Ageing-associated long non-coding RNA extends lifespan and reduces translation in non-dividing cells.

Genomes produce widespread long non-coding RNAs (lncRNAs) of largely unknown functions. We characterize aal1 (ageing-associated lncRNA), which is induced in quiescent fission yeast cells. Deletion of aal1 shortens the chronological lifespan of non-dividing cells, while ectopic overexpression prolongs their lifespan, indicating that aal1 acts in trans. Overexpression of aal1 represses ribosomal-protein gene expression and inhibits cell growth, and aal1 genetically interacts with coding genes functioning in protein translation. The aal1 lncRNA localizes to the cytoplasm and associates with ribosomes. Notably, aal1 overexpression decreases the cellular ribosome content and inhibits protein translation. The aal1 lncRNA binds to the rpl1901 mRNA, encoding a ribosomal protein. The rpl1901 levels are reduced ~2-fold by aal1, which is sufficient to extend lifespan. Remarkably, the expression of the aal1 lncRNA in Drosophila boosts fly lifespan. We propose that aal1 reduces the ribosome content by decreasing Rpl1901 levels, thus attenuating the translational capacity and promoting longevity. Although aal1 is not conserved, its effect in flies suggests that animals feature related mechanisms that modulate ageing, based on the conserved translational machinery.

RNA, Long Noncoding↗

PubMed1998

Telomerase activity and expression of telomerase RNA component and telomerase catalytic subunit gene in cervical cancer.

Telomerase, a ribonucleoprotein complex that includes the telomerase RNA component (hTR) and the telomerase catalytic subunit gene (hTERT) product, has been shown to be activated in the majority of cancer tissues and immortalized cells. To study telomerase activation during the progression of cervical cancer, the expression of hTR and hTERT RNAs in tissues of various stages of cervical cancer was analyzed using the in situ hybridization method and compared with proliferative activity as estimated by Ki-67 immunostaining. To test whether expression of these components is reflected in enzyme activity, we determined the levels of the RNAs in cervical cancer and normal tissues and in primary and immortal keratinocytes by reverse transcription-polymerase chain reaction and RNase protection assays and compared the results to telomerase activities as detected by telomeric repeat amplification protocol assay. In situ hybridization signals of hTR and hTERT were present not only in carcinoma tissues but also in normal epidermal layers. In many adenocarcinoma and fewer squamous cell carcinoma tissues, both signals were focally increased where high proliferative activity was present at the stages of dysplasia/metaplasia, in situ carcinoma, and invasive carcinoma. The level of bTERT, as quantitated by RNase protection assay, was not different between cancer and control tissues or immortal and a subset of primary keratinocytes and did not correlate with telomerase activity. These results indicate that expression of hTR and bTERT is up-regulated in at least a subset of neoplastic cells at an early stage of carcinogenesis and that unidentified factors, such as the modulation or coordination of its protein level with other products, may contribute to the activation of telomerase in cervical cancer.

Cell Division↗

PubMed1998

A 68-nucleotide sequence within the 3' noncoding region of simian hemorrhagic fever virus negative-strand RNA binds to four MA104 cell proteins.

The 3' noncoding region (NCR) of the negative-strand RNA [3'(-)NCR RNA] of the arterivirus simian hemorrhagic fever virus (SHFV) is 209 nucleotides (nt) in length. Since this 3' region, designated 3'(-)209, is the site of initiation of full-length positive-strand RNA and is the template for the synthesis of the 5' leader sequence, which is found on both full-length and subgenomic mRNAs, it is likely to contain cis-acting signals for RNA synthesis and to interact with cellular and viral proteins to form replication complexes. Gel mobility shift assays showed that cellular proteins in MA104 S100 cytoplasmic extracts formed two complexes with the SHFV 3'(-)209 RNA, and results from competition gel mobility shift assays demonstrated that these interactions were specific. Four proteins with molecular masses of 103, 86, 55, and 36 kDa were detected in UV-induced cross-linking assays, and three of these proteins (103, 55, and 36 kDa) were also detected by Northwestern blotting assays. Identical gel mobility shift and UV-induced cross-linking patterns were obtained with uninfected and SHFV-infected extracts, indicating that the four proteins detected are cellular, not viral, proteins. The binding sites for the four cellular proteins were mapped to the region between nt 117 and 184 (68-nt sequence) from the 3' end of the SHFV negative-strand RNA. This 68-nt sequence was predicted to form two stem-loops, SL4 and SL5. The 3'(-)NCR RNA of another arterivirus, lactate dehydrogenase-elevating virus C (LDV-C), competed with the SHFV 3'(-)209 RNA in competition gel mobility shift assays. UV-induced cross-linking assays showed that four MA104 cellular proteins with the same molecular masses as those that bind to the SHFV 3'(-)209 RNA also bind to the LDV-C 3'(-)NCR RNA and equine arteritis virus 3'(-)NCR RNA. However, each of these viral RNAs also bound to an additional MA104 protein. The binding sites for the MA104 cellular proteins were shown to be located in similar positions in the LDV-C 3'(-)NCR and SHFV 3'(-)209 RNAs. These data suggest that the binding sites for a set of the cellular proteins are conserved in all arterivirus RNAs and that these cell proteins may be utilized as components of viral replication complexes.

Animals↗

PubMed1991

Analysis of cDNAs of the proto-oncogene c-src: heterogeneity in 5' exons and possible mechanism for the genesis of the 3' end of v-src.

To further characterize the gene structure of the proto-oncogene c-src and the mechanism for the genesis of the v-src sequence in Rous sarcoma virus, we have analyzed genomic and cDNA copies of the chicken c-src gene. From a cDNA library of chicken embryo fibroblasts, we isolated and sequenced several overlapping cDNA clones covering the full length of the 4-kb c-src mRNA. The cDNA sequence contains a 1.84-kb sequence downstream from the 1.6-kb pp60c-src coding region. An open reading frame of 217 amino acids, called sdr (src downstream region), was found 105 nucleotides from the termination codon for pp60c-src. Within the 3' noncoding region, a 39-bp sequence corresponding to the 3' end of the RSV v-src was detected 660 bases downstream of the pp60c-src termination codon. The presence of this sequence in the c-src mRNA exon supports a model involving an RNA intermediate during transduction of the c-src sequence. The 5' region of the c-src cDNA was determined by analyzing several cDNA clones generated by conventional cloning methods and by polymerase chain reaction. Sequences of these chicken embryo fibroblast clones plus two c-src cDNA clones isolated from a brain cDNA library show that there is considerable heterogeneity in sequences upstream from the c-src coding sequence. Within this region, which contains at least 300 nucleotides upstream of the translational initiation site in exon 2, there exist at least two exons in each cDNA which fall into five cDNA classes. Four unique 5' exon sequences, designated exons UE1, UE2, UEX, and UEY, were observed. All of them are spliced to the previously characterized c-src exons 1 and 2 with the exception of type 2 cDNA. In type 2, the exon 1 is spliced to a novel downstream exon, designated exon 1a, which maps in the region of the c-src DNA defined previously as intron 1. Exon UE1 is rich in G+C content and is mapped at 7.8 kb upstream from exon 1. This exon is also present in the two cDNA clones from the brain cDNA library. Exon UE2 is located at 8.5 kb upstream from exon 1. The precise locations of exons UEX and UEY have not been determined, but both are more than 12 kb upstream from exon 1. The existence and exon arrangements of these 5' cDNAs were further confirmed by RNase protection assays and polymerase chain reactions using specific primers. Our findings indicate that the heterogeneity in the 5' sequences of the c-src mRNAs results from differential splicing and perhaps use of distinct initiation sites. All of these RNAs have the potential of coding for pp60c-src, since their 5' exons are all eventually joined to exon 2.

Amino Acid Sequence↗

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↗

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↗

PubMed2025

LncCE: Landscape of Cellularly-elevated lncRNAs in Single Cells Across Normal and Cancer Tissues.

Long non-coding RNAs (lncRNAs) have emerged as significant players in maintaining the morphology and function of tissues and cells. The precise regulatory effectiveness of lncRNAs is closely associated with their spatial expression patterns across tissues and cells. Here, we propose the Cellularly-Elevated LncRNA (LncCE) resource to systematically explore cellularly-elevated (CE) lncRNAs across normal and cancer tissues at single-cell resolution. LncCE encompasses 87,946 entries of CE lncRNAs of 149 cell types by analyzing 181 single-cell RNA sequencing datasets, involving 20 fetal normal tissues, 59 adult normal tissues, 32 adult cancer types, and 5 pediatric cancer types. Two main search options are provided via a given lncRNA name or cell type. The results emphasize both qualitative and quantitative expression features of lncRNAs across different cell types, their co-expression with protein-coding genes, and their involvement in biological functions. In particular, LncCE provides quantitative visualizations of lncRNA expression changes in cancers compared to control samples, as well as clinical associations with patients' overall survival. Together, LncCE offers an extensive, quantitative, and user-friendly interface to create a CE expression atlas for lncRNAs across normal and cancer tissues at the single-cell level. The LncCE database is available at http://bio-bigdata.hrbmu.edu.cn/LncCE.

RNA, Long Noncoding↗

PubMed2025

Constructing epigenetic regulatory landscapes of plant lncRNAs-an exploration utilizing the novel specialized platform PERlncDB.

Long non-coding RNAs (lncRNAs), once overlooked as transcriptional byproducts, are now recognized for their crucial roles in plant growth, development, and stress responses, with increasing focus on their epigenetic regulation. However, studies investigating epigenomic signals to explore the functions of lncRNAs in plants remain relatively limited. This study collected a comprehensive dataset of over 160 000 high-quality lncRNAs from 19 representative plant species and integrated 6715 ChIP-seq, BS-seq, and RNA-seq datasets to analyze epigenomic patterns at lncRNA loci. Results showed elevated DNA methylation in lncRNA regions. The highest levels occurred in transposable element-associated lncRNAs. Additionally, activating histone modifications at lncRNA loci showed tissue specificity, with epigenetic preferences differed from those at protein-coding gene (PCG) loci. Differential site analysis in epigenetic mutants further highlighted the selective regulation of lncRNA loci by specific epigenetic factors. To facilitate research, we developed PERlncDB, a platform that provides species-specific lncRNA browsing, epigenetic annotation, cross-species conservation analysis, and visualization of epigenomic landscapes. Case studies on MARS and LINC-AP2 emphasized the platform's utility. Conserved epigenetic mechanisms regulating lncRNAs across species, exemplified by a syntenic conserved MET1-regulated lncRNA pair in Arabidopsis and tomato, suggested the stability of regulatory mechanisms underlying lncRNA functions. This work provides critical insights and resources for understanding plant lncRNA epigenetic regulation.

RNA, Long Noncoding↗

PubMed2026

A Comparative Analysis of the Methylation Status of Non-Coding RNA Promoters in Fibroid and Matched Myometrium.

Uterine fibroids exhibit dysregulated expression of non-coding RNAs (ncRNAs), although the underlying mechanisms remain incompletely understood. We investigated promoter DNA methylation and its relationship with ncRNA expression in fibroids. Genomic DNA from eight paired fibroid and matched myometrial tissues was analyzed using MeDIP-chip to identify differentially methylated ncRNA promoters. Selected candidates were validated by methylation-specific PCR (MSP) in 16 paired samples, and transcript expression was assessed by qRT-PCR in 68-94 paired specimens. MeDIP-chip identified 538 lncRNAs and 61 miRNAs with differential promoter methylation, including 300 hypermethylated and 238 hypomethylated lncRNAs and 47 hypermethylated and 14 hypomethylated miRNAs. Promoter methylation was not significantly correlated with transcript expression (r = -0.1224). MSP confirmed hypermethylation of LINC-PINT and MIR9-3 and hypomethylation of WT1-AS and TTLL10-AS1. Correspondingly, LINC-PINT and MIR9-3 expression was decreased, whereas WT1-AS and TTLL10-AS1 expression was increased in fibroids. However, LINC-PINT and TTLL10-AS1 methylation did not fully correspond with MeDIP-chip findings. These results reveal widespread ncRNA promoter methylation alterations in uterine fibroids but demonstrate that genome-wide methylation does not consistently predict transcript expression, highlighting the complexity of ncRNA epigenetic regulation and the importance of locus-specific validation.

Humans↗

PubMed2025

Expression analysis of LINC00671 and LINC01913 long non-coding RNAs in gastric cancer patients and their correlation with EMT markers.

BACKGROUND: Long-chain non-coding RNAs (lncRNAs) play various roles in the regulation of gene expression at the levels of transcription and translation, and epigenetic modification. Dysregulation of lncRNAs is associated with various malignancies, including cancer. lncRNAs have been demonstrated to regulate critical biological processes in cancer cells, such as apoptosis, proliferation, migration, and invasion. They also play essential roles in the development of gastric cancer (GC). However, the clinical significance and biological function of many lncRNAs remain unexplored in GC progression. This study aimed to evaluate the expression profiles of LINC00671 and LINC01913 in GC patients and investigate their correlation with epithelial-to-mesenchymal transition (EMT) markers. METHOD: The real-time PCR technique was applied to measure the expression levels of the selected lncRNAs (LINC01913 and LINC00671) and EMT-related mRNAs (MAMLs and MMP-13) in 83 tumor and adjacent normal tissues obtained from GC patients. RESULT: A significant reduction in LINC00671 expression was observed in 55.4% of tumor tissues, while elevated expression of LINC01913 (41%), MMP13 (56.6%), and MAML1 (44.6%) was detected, representing the proportion of samples with dysregulated expression relative to matched normal tissues. Dysregulation of these genes was significantly associated with various clinicopathological features (P < 0.05), supporting a potential link between these lncRNAs and EMT processes in GC. CONCLUSION: The observed associations between LINC00671, LINC01913, and EMT-related genes suggest their potential as prognostic biomarkers for treatment response in GC patients.

Humans↗

PubMed2026

LINC01871-Mediated Sensitivity to Cyclin-Dependent Kinase 4/6 Inhibitors in Human Breast Cancer.

Breast cancer remains the most frequently diagnosed malignancy in women, and resistance to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors limits long-term treatment efficacy. This study aimed to identify long non-coding RNAs (lncRNAs) associated with predicted sensitivity to CDK4/6 inhibitors and to investigate their biological functions in breast cancer. Transcriptomic data from The Cancer Genome Atlas (TCGA) and drug sensitivity data from the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) database were integrated, and drug sensitivity was predicted using the oncoPredict algorithm. Candidate lncRNAs were identified through differential expression analysis, weighted gene co-expression network analysis, prognostic analysis, and machine learning. The biological functions of LINC01871 were subsequently evaluated using in vitro and in vivo experiments. Sixty-two lncRNAs associated with predicted sensitivity to ribociclib and palbociclib were identified, and six core lncRNAs were selected. LINC01871 showed the highest discriminatory performance for predicted drug sensitivity. Overexpression of LINC01871 was associated with increased sensitivity of breast cancer cells to ribociclib and palbociclib, inhibition of cell proliferation, promotion of apoptosis, and suppression of nuclear factor kappa B (NF-κB) signaling. Single-cell transcriptomic analysis demonstrated high LINC01871 expression in T cells and natural killer (NK) cells, while transcriptome-based immune infiltration analyses showed that high LINC01871 expression was associated with increased immune infiltration. These findings identify LINC01871 as a candidate biomarker of sensitivity to CDK4/6 inhibitors and demonstrate its tumor-suppressive effects in breast cancer. Further clinical and mechanistic studies are required to validate its predictive value and therapeutic relevance.

Humans↗

PubMed2000

The H19 endodermal enhancer is required for Igf2 activation and tumor formation in experimental liver carcinogenesis.

The expression of the linked but reciprocally imprinted Igf2 and H19 genes is activated in adult liver in the course of tumor development. By in situ hybridization analysis we have shown that both the Igf2 and H19 RNAs are expressed in the majority of the neoplastic nodules, and that hepatocellular carcinomas are developed in an experimental model of liver carcinogenesis. H19 is also highly activated in smaller and less distinct hyperplastic regions. The few neoplastic areas showing Igf2 but no H19 RNA display loss of the maternally inherited allele at the Igf2/H19 locus. These data are compatible with the existence of a common activation mechanism of these two genes during liver carcinogenesis and with a stronger H19 induction in the pre-neoplastic lesions. By using mice carrying a deletion of the H19 endodermal enhancer, we show that this regulatory element is necessary for the activation of the Igf2 and H19 genes upon induction of liver carcinogenesis. Furthermore, multiple sites of the H19 endodermal enhancer region become hypersensitive to DNase I when the carcinogenesis process is induced. Lastly, liver tumors developed in mice paternally inheriting the H19 enhancer deletion are found to have marked growth delays, increased frequency of apoptotic nuclei, and lack of Igf2 mRNA expression, thus indicating that this regulatory element plays a major role in the progression of liver carcinogenesis, since it is required for the activation of the anti-apoptotic Igf2 gene.

Animals↗