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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

Comparative transcriptome analysis reveals ncRNA-mediated regulatory networks associated with muscle crispiness in grass carp.

Non-coding RNAs (ncRNAs) have been demonstrated to be involved in muscle development and to function as key regulators. However, the molecular mechanism underlying muscle crispiness in grass carp (GC) remains poorly understood, and whether these ncRNAs are involved in its regulation is still unknown. In the current investigation, differentially expressed (DE) RNAs (including lncRNAs, circRNAs, miRNAs, and mRNAs) were identified; concomitantly, target genes prediction was conducted, and functional and signaling pathway enrichment analyses were performed. Pathways related to muscle crispiness were identified, and the competitive endogenous RNA (ceRNA) (lncRNA/circRNA-miRNA-mRNA) regulatory network was further constructed. The results showed that a total of 126 DE-lncRNAs, 17 DE-circRNAs, 329 DE-miRNAs, and 442 DE-mRNAs were identified in muscle tissues of both the GC and crisp grass carp (CGC). GO and KEGG enrichment analyses revealed that target genes of DE-ncRNAs were significantly enriched in signaling pathways, including structural constituents of muscle, apoptosis, oxidative phosphorylation, and regulation of actin cytoskeleton, suggesting that these pathways may be involved in muscle texture remodeling. Subsequently, DE-RNAs enriched in related pathways were identified, and a core ceRNA regulation network comprising 3 lncRNAs, 4 circRNAs, 3 miRNAs, and 17 mRNAs was constructed. Additionally, 10 DE-RNAs from randomly selected groups were validated by qRT-PCR. Our findings not only provide scientific evidence elucidating the molecular mechanisms underlying muscle crispiness in GC but also establish a foundation for studying changes in muscle textural qualities across other fish species.

Animals↗

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

First insights into the miRNA landscape of Tursiops truncatus milk reveal shared dominant microRNA families with terrestrial mammals.

MicroRNAs (miRNAs) are small non-coding RNAs that play crucial regulatory roles in gene expression in metazoans. While the miRNA repertoire and relative abundances have been extensively studied in terrestrial mammals, no information was available for the milk of marine mammals. Here, we present the first characterization of the miRNA genomic landscape and abundance in milk in the bottlenose dolphin (Tursiops truncatus). Using a sequence-based comparative approach, we identified 186 conserved miRNA families comprising 354 high-confidence precursors in the dolphin genome. Comparative analysis across 52 cetacean genomes revealed a small number of lineage-specific loss events, such as mir-187 in Delphinidae, and the absence of nine miRNA families in all cetaceans. Small RNA sequencing from pooled milk samples confirmed the detectable abundance of 119 miRNAs, with a landscape dominated by mir-148, let-7, mir-8, and mir-21, collectively accounting for over 70% of total miRNA reads. These dominant families include miRNAs frequently reported in the milk of terrestrial mammals, suggesting qualitative similarity in the major milk miRNA repertoire between dolphin and terrestrial mammals. These findings should be interpreted as a first sequencing-supported exploratory characterization of dolphin milk miRNAs.

Animals↗

PubMed2026

A novel peptide encoded by circTLL1 drives osimertinib resistance in lung cancer by modulating the NT5C2/Ras/PI3K axis.

BACKGROUND: Acquired resistance to osimertinib, a third-generation EGFR tyrosine kinase inhibitor, remains a major clinical challenge in the treatment of non-small cell lung cancer (NSCLC). Although circular RNAs (circRNAs) have been increasingly implicated in drug resistance, most studies have focused on their canonical role as microRNA sponges, while their capacity to encode functional micropeptides remains largely unexplored. This study aimed to identify novel circRNAs involved in osimertinib resistance and to characterize their regulatory functions at the protein level. METHODS: Osimertinib-resistant (OR) NSCLC cell lines were established and validated. High-throughput RNA sequencing was performed to compare the circRNA expression profiles between parental and OR cells. The function of the candidate circRNA was assessed through a series of in vitro and in vivo experiments, including cell viability assays, apoptosis analysis, and xenograft mouse models. Mechanistic investigations involved mass spectrometry, co-immunoprecipitation and western blotting to explore its protein-coding potential and downstream signaling pathways. RESULTS: We identified a novel circRNA, termed circTLL1, that was stably and significantly upregulated in OR-NSCLC cells. Functionally, overexpression of circTLL1 promoted osimertinib resistance, whereas its knockdown restored drug sensitivity both in vitro and in vivo. Mechanistically, we discovered that circTLL1 harbors an open reading frame (ORF) that is translated into a novel 90-amino-acid protein, which we designated circTLL1-90aa. Further investigation revealed that circTLL1-90aa directly interacts with and promotes the degradation of 5'-nucleotidase, cytosolic II (NT5C2), thereby uncoupling nucleotide metabolism from its normal regulatory constraints. The consequent downregulation of NT5C2 leads to elevated GTP levels and leading to the sustained activation of the downstream Ras/PI3K/AKT signaling pathway. CONCLUSION: Our findings unveil a previously unrecognized circRNA/micropeptide/metabolism cascade underlying osimertinib resistance. The identification of the circTLL1-90aa/NT5C2/Ras/PI3K axis not only expands the functional repertoire of the non-coding genome but also provides new insights into the complexity of drug resistance. Given its selective upregulation in resistant cells, circTLL1-90aa holds promise both as a predictive biomarker for treatment stratification and as an actionable therapeutic target, offering a novel strategy to overcome osimertinib resistance in NSCLC patients.

Pyrimidines↗

PubMed2026

Transcriptomic changes in the gut mucosa of fasting northern elephant seal pups reveal immune modulation during early microbiome establishment.

Fasting is an integral component of the life-history of many species. Following abrupt weaning, northern elephant seal pups (Mirounga angustirostris) undergo an extended post-weaning fast of approximately 60 days. During this period, enteric bacterial diversity increases, suggesting that host immune regulation may facilitate the establishment of microbial communities. However, the molecular processes occurring within the intestinal mucosa during this transition remain poorly understood. To investigate these mechanisms, we characterized transcriptional changes in the enteric mucosa of male and female northern elephant seal pups sampled at weaning and after one month of fasting. Total RNA isolated from rectal swabs was sequenced and aligned to the Mirounga angustirostris reference genome. Differential gene expression and gene set enrichment analyses were used to identify genes and pathways associated with fasting and sex-specific responses. Fasting was accompanied primarily by transcriptional downregulation, including genes involved in antimicrobial defense, inflammation, protein turnover, and epithelial remodeling. In contrast, several genes associated with B-cell activity and immune recognition were upregulated. Gene Set Enrichment Analysis revealed coordinated activation of immune-regulatory pathways indicating dynamic modulation of intestinal immunity rather than generalized immune suppression. Pronounced sex-specific differences were also observed. Male pups exhibited transcriptional patterns consistent with enhanced immune tolerance, whereas females showed broader immune-pathway activation, including enrichment of pro-inflammatory and stress-response pathways. Several non-coding RNAs also displayed sex-specific changes in expression. Together, these findings suggest that fasting induces transcriptional remodeling of the gut and may contribute to immune regulation during a critical period of microbiome establishment in northern elephant seal pups.

Animals↗

PubMed2026

m6A RNA modification and its emerging roles in diseases: recent advances and therapeutic implications.

BACKGROUND: In the recent past, insights in post transcriptional regulation of gene expression have profoundly reshaped our understanding of the molecular mechanisms underlying health and disease. This paradigm shift largely stems from the emerging field of epitranscriptomics, which highlights the pivotal role of chemical RNA modifications. While more than 170 distinct chemical modifications on the RNA are known, the m6A modification is the most abundant internal mRNA modification in higher eukaryotic cells, present not only on protein coding transcripts but also on non-coding RNAs, regulated by “writers”, “erasers”, and “readers” that together modulate alternative splicing, nuclear export, translation efficiency, and mRNA stability. MAIN BODY: This review addresses an important gap by presenting a multilayered regulatory framework that catalogs the full repertoire of m6A machinery and uniquely reveals how non-coding RNAs, transcription factors, histone modifications, and chromatin remodelers governs the spatiotemporal specificity of m6A modification. We explore how dysregulation of m6A modification and its regulatory proteins contribute to the development and progression of various diseases such as cardiovascular disease, neurological disorders, cancer, and type 2 diabetes through context-dependent modulation of gene networks. Furthermore, we present an integrative overview of the therapeutic pipeline, tracing the development of small-molecule inhibitors targeting m6A regulators, thus bridging a crucial link between fundamental mechanisms and new therapies. CONCLUSIONS: Overall, this review integrates current findings and emerging insights to provide a comprehensive understanding of m6A biology. By linking upstream regulatory mechanisms with downstream pathological consequences and therapeutic interventions, we highlight the potential of targeting the epitranscriptome for clinical applications.

Humans↗

PubMed2003

Organic anion and cation transporters occur in pairs of similar and similarly expressed genes.

Organic anion and cation transporters (OATs, OCTs, OCTNs, and ORCTLs), transmembrane proteins essential to renal xenobiotic excretion, are encoded by a group of related genes. As yet there have been no studies of the transcriptional regulation of this important gene family. While such studies have traditionally been labor-intensive, comparative genomics approaches are now available that have proven reliable guides to critical regulatory elements. We report here the genomic sequencing of murine OAT1 (the cDNA of which was originally cloned by us as NKT) and OAT3 (Roct), and derivation of phylogenetic footprints (evolutionarily conserved non-coding sequences) by comparison to the human genome. We find binding sites within these footprints for several transcription factors implicated in kidney development, including PAX1, PBX, WT1, and HNF1. Additionally, we note that OATs and OCTs occur in the human and mouse genomes as tightly linked pairs (OAT1 and OAT3, UST3 and OAT5, OAT4 and URAT1/RST, OCT1 and 2, OCTN1 and 2, ORCTL3 and 4) that are also close phylogenetic relations, with Flipt1 and 2, and OAT2 the only unpaired family members. Finally, we find that pair-members have similar tissue distributions, suggesting that the pairing might exist to facilitate the co-regulation of the genes within each pair.

5' Flanking Region↗

PubMed2026

TET2 promotes monocyte inflammatory activation in asthma via ALKBH5-m6A regulation and PI3K signaling: evidence from m6A-SNP and single-cell analyses.

Asthma is a complex inflammatory airway disease with strong genetic determinants, yet the functional relevance of most asthma-associated non-coding variants remains unclear. Emerging evidence suggests that N6-methyladenosine (m6A) modification may serve as a critical epitranscriptomic link between genetic variation and immune regulation. In this study, we aimed to systematically identify functionally relevant m6A-regulated genes in asthma by integrating large-scale GWAS data, m6A-SNP annotations, and single-cell transcriptomic analyses, and to investigate their roles in monocyte-driven airway inflammation. We identified TET2 as a key m6A-regulated gene associated with both asthma and lung function, which was selectively upregulated in monocytes during asthma and accompanied by activation of inflammatory and PI3K signaling pathways. Mechanistic experiments further demonstrated that inflammatory stimulation induced ALKBH5 expression, reduced m6A modification of TET2 mRNA, and increased TET2 protein levels, thereby promoting PI3K/AKT signaling and pro-inflammatory cytokine production, whereas inhibition of TET2 or ALKBH5 attenuated these effects. Collectively, these findings demonstrate that ALKBH5-mediated m6A regulation of TET2 enhances PI3K/AKT signaling in monocytes, thereby promoting inflammatory responses in asthma. Our study establishes TET2 as a key m6A-regulated gene linking genetic susceptibility to monocyte-driven inflammation, and highlights the ALKBH5-m6A-TET2 axis as a potential therapeutic target for modulating aberrant immune responses in asthma.

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↗

PubMed2024

Exploring the transcriptional cooperation between RUNX2 and its associated elncRNA RAIN.

Recent insights into the mechanisms controlling gene expression identified enhancer-associated long non-coding RNAs (elncRNAs) as master players of transcription in cancers. RUNX2, a mammalian RUNT-related transcription factor, is increasingly recognized in cancer biology for its role in supporting survival and progression also in thyroid cancer (TC). We recently identified, within the RUNX2 locus, a novel elncRNA that we named RAIN (RUNX2 associated intergenic lncRNA). We showed that RAIN and RUNX2 expression correlate in TC, both in vitro and in vivo, and that RAIN promotes RUNX2 expression by interacting with and affecting the activity of the RUNX2 P2 promoter through two distinct mechanisms. Here, we took forward these observations to explore the genome-wide transcriptional function of RAIN and its contribution to the RUNX2-dependent gene expression program in TC. By combining multiple omics data, we demonstrated that RAIN functionally cooperates with RUNX2 to the regulation of a subset of functionally related genes involved in promoting matrix remodeling, migration, and loss of differentiation. We showed that RAIN interacts with RUNX2 and its expression is required for the efficient recruitment of this TF to its target regulatory regions. In addition, our data revealed that besides RUNX2, RAIN governs a hierarchically organized complex transcriptional program by controlling a core of cancer-associated TFs that, in turn, orchestrate the expression of downstream genes. This evidence indicates that the functional cooperation observed between RAIN and RUNX2 can be a diffuse work mechanism for this elncRNA.

Core Binding Factor Alpha 1 Subunit↗

PubMed2017

Genome-wide analysis suggests a differential microRNA signature associated with normal and diabetic human corneal limbus.

Small non-coding RNAs, in particular microRNAs (miRNAs), regulate fine-tuning of gene expression and can impact a wide range of biological processes. However, their roles in normal and diseased limbal epithelial stem cells (LESC) remain unknown. Using deep sequencing analysis, we investigated miRNA expression profiles in central and limbal regions of normal and diabetic human corneas. We identified differentially expressed miRNAs in limbus vs. central cornea in normal and diabetic (DM) corneas including both type 1 (T1DM/IDDM) and type 2 (T2DM/NIDDM) diabetes. Some miRNAs such as miR-10b that was upregulated in limbus vs. central cornea and in diabetic vs. normal limbus also showed significant increase in T1DM vs. T2DM limbus. Overexpression of miR-10b increased Ki-67 staining in human organ-cultured corneas and proliferation rate in cultured corneal epithelial cells. MiR-10b transfected human organ-cultured corneas showed downregulation of PAX6 and DKK1 and upregulation of keratin 17 protein expression levels. In summary, we report for the first time differential miRNA signatures of T1DM and T2DM corneal limbus harboring LESC and show that miR-10b could be involved in the LESC maintenance and/or their early differentiation. Furthermore, miR-10b upregulation may be an important mechanism of corneal diabetic alterations especially in the T1DM patients.

Adult↗

PubMed2026

Comparative transcriptome analysis of Qinchuan and Wagyu cattle reveals lnc11599 as a negative regulator of intramuscular fat deposition.

BACKGROUND: Intramuscular fat (IMF) content is a critical factor determining beef quality, influenced by various factors including breed and age. However, the regulatory role of long non-coding RNAs (lncRNAs) in IMF deposition remains unclear. METHODS: This study investigated IMF deposition in the longissimus dorsi muscle of one- and two-year-old Qinchuan and Wagyu cattle through histological examination and fat content measurement. Based on transcriptome sequencing data of intramuscular fat tissue, differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify lncRNAs associated with IMF deposition. The effects of a key candidate lncRNA on the adipogenic differentiation of cattle intramuscular preadipocytes were further examined. RESULTS: Results showed that Wagyu cattle exhibited stronger IMF deposition capacity than Qinchuan cattle across all age groups, with IMF content increasing with age in both breeds. We identified 7,910 lncRNAs from intramuscular fat tissue transcriptome data, including 6,455 novel lncRNAs. Through integrated differential expression analysis and WGCNA, 88 lncRNAs closely associated with IMF deposition were screened from two-year-old Qinchuan and Wagyu cattle. Notably, lnc11599 was significantly upregulated in Qinchuan cattle intramuscular fat tissue, but its expression decreased during intramuscular preadipocyte differentiation. Functional experiments demonstrated that lnc11599 knockdown enhanced adipogenic differentiation capacity, manifested as a highly significant increase in lipid accumulation, upregulation of key adipogenic genes at the mRNA level, together with increases in total fatty acid content and unsaturated fatty acid proportion. CONCLUSIONS: This study established the lncRNA expression profiles in intramuscular fat tissue of Qinchuan and Wagyu cattle across different developmental stages, and demonstrated that lnc11599 acts as a negative regulator of intramuscular fat deposition. These findings provide new directions for elucidating the mechanisms of cattle IMF deposition and offer potential targets for genetic improvement of beef quality.

Animals↗

PubMed2026

A Novel piRNA-Mediated Epigenetic Axis: piR-36241 Exacerbates Pulpitis by Silencing the Protective Receptor ADGRG2 in Human Dental Pulp Stem Cells.

BACKGROUND: Pulpitis, a prevalent inflammatory dental disease, primarily results from bacterial infection, yet its epigenetic regulatory mechanisms remain poorly understood. PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs known to maintain genomic stability, have not been investigated in the context of pulpitis. OBJECTIVE: This study aimed to profile piRNA expression patterns in pulpitis and to elucidate the functional role and underlying mechanism of a specific piRNA, piR-36241 and its target gene ADGRG2 in disease progression. METHODS: piRNA and mRNA sequencing were performed on pulp tissues from patients with irreversible pulpitis and healthy controls. Potential piRNA targets were predicted bioinformatically. The interaction between piR-36241 and the 3'UTR of ADGRG2, an orphan adhesion G protein-coupled receptor (GPCR), was validated using dual-luciferase reporter assay, quantitative Real-Time PCR (qRT-PCR), fluorescence in situ hybridization (FISH), Western blot (WB), hematoxylin-eosin staining (HE), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Functional analyses were conducted in LPS-stimulated human dental pulp cells (HDPCs) through gain-of-function and rescue experiments. RESULTS: We identified a distinct piRNA expression profile in pulpitis, with 21 piRNAs differentially expressed. piR-36241 was notably upregulated. It directly targeted the 3'UTR of ADGRG2 and suppressed its expression. ADGRG2, hypothesised to exert protective and homeostatic functions, was downregulated in pulpitis tissues and LPS-induced HDPCs. Overexpression of piR-36241 inhibited ADGRG2 expression and promoted the secretion of pro-inflammatory cytokines (IL-6, IL-8). Conversely, knockdown of ADGRG2 similarly enhanced inflammatory responses. Rescue experiments demonstrated that piR-36241 primarily regulates inflammation through ADGRG2 silencing. CONCLUSION: Our study reveals a novel pathogenic axis in pulpitis whereby upregulation of piR-36241 exacerbates inflammatory progression by repressing the protective receptor ADGRG2. These findings provide the first evidence of piRNA-mediated epigenetic regulation in pulpitis and highlight the piR-36241/ADGRG2 pathway as a potential therapeutic target for preserving pulp vitality.

Humans↗

PubMed2025

MicroRNA-122 overexpression suppresses the colon cancer cell proliferation by downregulating the astrocyte elevated gene-1/metadherin oncoprotein.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that regulate essential cellular functions, such as cell adhesion, proliferation, migration, invasion, and programmed cell death, and therefore, alterations in miRNAs can contribute to carcinogenesis. Previous studies have shown that miRNA-122 is abundant in the liver and regulates cell proliferation, migration, and apoptosis. However, the expression pattern and mechanism of actions of miR-122 remain primarily unknown in colon cancer. METHODS: In this study, we analyzed The Cancer Genome Atlas Colon Adenocarcinoma (TCGA-COAD) database to assess the clinical significance of astrocyte elevated gene-1 (AEG-1)/metadherin (MTDH) and miR-122 in colon cancer. MiR-122 overexpression studies were performed in HCT116, SW480, and SW620 cell lines. Dual-luciferase assay was carried out to confirm the interaction between AEG-1 and miR-122. In vivo-JetPEI-transfection reagent was used for in-vivo transient transfection of miR-122 in the AOM/DSS-induced colon tumor mouse model. RESULTS: Our results demonstrate that miR-122 was downregulated in colon cancer cells, and it influences the expressions of apoptotic factors and inflammatory cytokines. MiR-122 overexpression in HCT116, SW480, and SW620 cells showed upregulation of Caspase 3, Caspase 9, and BAX and decreased expression of BCL2, which are pro-apoptotic and anti-apoptotic members that maintain a ratio between cellular survival and cell death. In vivo transient transfection of miR-122 mimic in AOM/DSS induced colon tumor mouse model showed less inflammation and disease activity. The TCGA-COAD data indicated that AEG-1 expression was higher in patients with low expression of miR-122 and lower AEG-1 expression in patients with higher expression miR-122. CONCLUSION: Our findings highlight the key role of miR-122 in the high grade of colonic inflammation, and possibly in colon cancer, and the use of miR-122 mimic might be a therapeutic option.

MicroRNAs↗

PubMed2026

Characterization of the genomic and transcriptomic landscape of invasive non-mucinous lung adenocarcinoma based on IASLC grading.

BACKGROUND: The IASLC grading system has prognostic utility and potential therapeutic implications in invasive non-mucinous lung adenocarcinoma (LUAD), but the molecular basis underlying the grading spectrum remains unclear. METHODS: We performed whole-genome sequencing in 138 Chinese patients with invasive non-mucinous LUAD and RNA sequencing of 96 matched tumor-normal tissue pairs to systematically characterize the molecular features across grades, including coding driver events, mutational signatures, non-coding regulatory disruptions, and transcriptional programs. RESULTS: Compared with Grade 1-2 tumors, Grade 3 LUADs exhibited heightened invasive potential, manifested by more advanced stage, more frequent spread through air spaces, and independently worse survival. Grade 3 tumors had elevated tumor mutational burden and were enriched for alterations in genome maintenance and cell-cycle genes, including TP53, as well as genes implicated in DNA damage response, including ZFHX4. APOBEC-associated mutagenesis was selectively enriched in Grade 3 tumors independent of smoking status, consistent with an instability-associated phenotype. Recurrent non-coding regulatory disruptions affected lung lineage-defining genes, particularly surfactant-associated genes, and were correlated with reduced expression. Transcriptomic profiling revealed epithelial dedifferentiation, loss of pulmonary homeostatic programs, and activation of proliferative and stress-related pathways. Notably, MUC16 emerged as a convergent event linking genomic and transcriptional dysregulation, with coding mutations associated with higher expression and increased expression in Grade 3 tumors correlating with the proportion of high-grade histologic patterns. CONCLUSIONS: These findings provide a molecular framework for the IASLC grading spectrum and identify Grade 3 LUAD as a distinct instability-associated and dedifferentiated biological state.

IASLC grading↗

PubMed2026

Uncovering hidden complexity in the Apis mellifera mitotranscriptome: a polyadenylation-centered perspective.

Mitochondrial transcription is gaining increasing attention as researchers seek to better understand the full coding potential of mitochondrial DNA (mtDNA). Emerging evidence suggests that mtDNA may encode additional elements beyond classical oxidative phosphorylation genes, pointing to a more complex transcriptional architecture than previously recognized. In this study, we explored the mitochondrial transcriptome of Apis mellifera (Insecta: Hymenoptera), with a particular focus on polyadenylation-associated features. Our analysis revealed that both sense and antisense transcripts undergo polyadenylation, although transcript abundance and poly(A) tail lengths varied markedly across mitochondrial genes. Several transcripts exhibited alternative isoforms, either extended or truncated, frequently including intergenic regions. These regions may represent functional non-coding elements or structural variants rather than conventional untranslated regions (UTRs). Interestingly, some transcripts also contained non-templated nucleotide additions particularly cytosine residues immediately upstream of the poly(A) tails. Monocistronic units that included portions of downstream intergenic regions were among the most abundantly represented, suggesting a possible regulatory role for these sequences. To experimentally validate our in silico findings, we performed RT-qPCR to assess relative gene expression and applied 3' RACE-PCR to define transcript boundaries. These approaches confirmed the presence of multiple transcript isoforms and supported the involvement of polyadenylation in shaping mitochondrial RNA diversity. Together, our findings reveal a previously underappreciated level of complexity in the A. mellifera mitochondrial transcriptome and highlight the potential regulatory significance of polyadenylation dynamics and intergenic region transcription.

Animals↗