The RNA methyltransferase methyltransferaselike protein 16 (METTL16) is upregulated in a large proportion of hepatocellular carcinoma (HCC), and its high expression is associated with poor clinical outcomes. METTL16 deletion inhibits HCC growth in vitro and in vivo. Referencing the structure of cinnamic acid, here we designed and synthesized a novel series of small molecular compounds, and found through bioactivity screening that compound 15a effectively reduced METTL16 level and modulated oncogenic PI3K/AKT pathway signaling. Compound 15a inhibited the proliferation and migration of HepG2 cells, and induced apoptosis in vitro. Furthermore, compound 15a significantly inhibited the growth of patient-derived HCC xenografts in nude mice with greater efficacy than the multi-kinase inhibitor lenvatinib. The promising efficacy and good biosafety profile of compound 15a enables us to further develop this compound for treating patients with HCC and possibly other cancers in clinic.

The eukaryotic initiation factor 5A2 gene (EIF5A2) is a highly conserved and multifunctional gene that significantly influences various cellular processes, including translation elongation, RNA binding, ribosome binding, protein binding and post-translational modifications. Overexpression of EIF5A2 is frequently observed in multiple cancers, where it functions as an oncoprotein. Additionally, EIF5A2 is implicated in drug resistance through the regulation of various molecular pathways. In the review, we describe the structure and functions of EIF5A2 in normal cells and its role in tumorigenesis. We also elucidate the molecular mechanisms associated with EIF5A2 in the context of tumorigenesis and drug resistance. We propose that the biological roles of EIF5A2 in regulating diverse cellular processes and tumorigenesis are clinically significant and warrant further investigation.

Long non‑coding RNAs (lncRNAs) are key regulators of gene expression, that can regulate a range of carcinogenic processes. Moreover, they exhibit stability in biological fluids, with some displaying tissue specificity. As their expression depends on specific conditions or is linked to the regulation of particular signaling pathways, lncRNAs are promising candidates for providing insights into the likely progression of the disease. This allows for the stratification of patients based on their risk of progression, making them potential prognostic biomarkers in various types of cancer. In addition, the tissue‑specific expression profile of lncRNAs renders them ideal candidates for detection, prognosis and monitoring of cancer progression. The present study aims to provide an overview of differentially expressed lncRNAs in Mexican patients with triple‑negative breast cancer (TNBC), a subtype of breast cancer. The aim was to identify potential prognostic biomarkers that can be applied to improve the clinical management of Mexican patients with TNBC. Human Transcriptome Array 2.0 microarrays were used to analyze the transcriptome of TNBC and luminal tumors, which are reported to have a good prognosis amongst aggressive tumor types. Subsequently, results from these microarrays were validated in a cohort from The Cancer Genome Atlas, an independent cohort of Mexican patients and in breast cancer cell lines (MCF7, ZR75, T47D, MDA‑MB‑231, MDA‑MB‑468 and BT20). A total of 746 differentially expressed transcripts were identified, including 102 lncRNAs in TNBC compared with luminal tumors. Among the lncRNAs with the most significant changes in expression levels, SOX9‑AS was highly expressed in TNBC, whereas the expression of Lnc‑peroxidasin‑3:1 (Lnc‑PXDN‑3:1), Lnc‑RNA Synapse Defective Rho GTPase Homolog (Lnc‑SYDE) and long intergenic non‑coding RNA (LINC)01087 were decreased. In addition, the low expression of lncRNA LINC01087, LINC02568, ACO22196, and lncRNA eosinophil granule ontogeny transcript (Lnc‑EGOT) was associated with poor overall survival (OS). Further analysis revealed that the high expression levels of Lnc‑PXDN‑3:1, Lnc RNA fibrous sheath interacting protein 1‑6:3 and (LINC)00182 were associated with reduced survival in patients with the luminal subtype of breast cancer. Similarly, low expression levels of lncRNAs such as GATA binding protein 3‑1 (Lnc‑GATA‑3‑1), LINC01087, and BX679671.1 in luminal subtypes of breast cancer, as well as LINC00504 and LncRNA rho guanine nucleotide exchange factor 38 intronic transcript 1 (Lnc‑ARHGEF38‑IT1) in basal subtypes have been linked to poorer survival. The interactions and functions of LINC01087 were then investigated, revealing the interaction of LINC01087 with RNAs and transcription factors, highlighting their potential involvement in the estrogen receptor pathway. The present study provided a detailed analysis of the expression of lncRNAs in TNBC, which highlights the role of lncRNAs as a biomarker in the survival outcomes of patients with breast cancer to improve the understanding of transcriptional regulation in TNBC.

Breast cancer (BC) has become the most common malignant tumor in women worldwide. This study was carried out to find and validate a novel molecular therapeutic target for BC.

Long non-coding RNA (lncRNA) AK023507 was selected as the study objects through microarray analysis. The function of lncRNA AK023507 was verified by various cell function experiments in vitro, subcutaneous tumorigenesis experiments, and lung metastasis model experiments in vivo. The RNA pull-down experiment and Western blot experiment were used to confirm the mechanism regulation pathway and the recovery experiment was used to verify it. TCGA datasets were used for clinical and immune function prediction analysis.

In vitro cell function tests and in vivo experiments suggested that overexpression of lncRNA AK023507 inhibited the proliferation and metastasis of BC cells. The RNA pull-down experiment and Western blot analysis validated that lncRNA AK023507 interacted with the dedicator of cytokinesis 4 (DOCK4) protein. Analysis of public databases predicted that DOCK4 is a potential prognostic risk factor associated with epithelial-mesenchymal transition (EMT) and central memory T cell (TCM) cellular immune infiltration.

LncRNA AK023507 inhibits the proliferation and metastasis of BC by regulating the DOCK4/β-catenin axis. This discovery will provide new potential therapeutic targets for BC.

Temozolomide (TMZ) is used in the treatment of glioblastoma (GBM). However, the primary obstacle remains the emergence of TMZ chemotherapy resistance. Non-POU domain-containing octamer-binding protein (NONO) and splicing factor proline/glutamine rich (SFPQ) are multifunctional nuclear proteins involved in genome stability and gene regulation. However, the specific role of NONO and SFPQ in TMZ resistance of GBM remains to be explored.

RNA-binding protein immunoprecipitation-microarray and RNA microarray of TMZ-resistant and parental cells were performed for the gain of HSD52. The effects of HSD52 on TMZ resistance were investigated through in vitro assays, intracranial xenograft, and GBM organoid models. The underlying mechanisms were explored by DNA methylation chip, RNA immunoprecipitation, RNA pull-down assays, among others. GBM clinical samples were rolled in to investigate the clinical significance of HSD52.

We identified a novel noncoding RNA, HSD52, that was highly expressed in TMZ-resistant GBM and facilitated the interaction between NONO and SFPQ. H3 ubiquitination attenuation and reduced DNA methyltransferase 1 (DNMT1) recruitment increased HSD52 transcription via DNA hypo-methylation. HSD52 formed an RNA duplex with UFM1 specific ligase 1 (UFL1) mRNA, thereby promoting NONO/SFPQ complex binding to UFL1 mRNA and enhancing its stability, and then contributed to TMZ resistance through activating the ataxia telangiectasia mutated signaling pathway. In vivo xenograft and GBM organoid models showed significant repression in tumor growth after HSD52 knockout with TMZ treatment. In GBM clinical samples, HSD52 was responsible for the malignant progression and TMZ resistance.

Our results revealed that HSD52 could serve as a promising therapeutic target to overcome TMZ resistance, improving the clinical efficacy of TMZ chemotherapy in GBM.

Cell-free RNAs (cfRNAs) can be detected in biofluids and have emerged as valuable disease biomarkers. Accurate identification of the fragmented cfRNA signals, especially those originating from pathological cells, is crucial for understanding their biological functions and clinical value. However, many challenges still need to be addressed for their application, including developing specific analysis methods and translating cfRNA fragments with biological support into clinical applications.

We present cfPeak, a novel method combining statistics and machine learning models to detect the fragmented cfRNA signals effectively. When test in real and artificial cfRNA sequencing (cfRNA-seq) data, cfPeak shows an improved performance compared with other applicable methods. We reveal that narrow cfRNA peaks preferentially overlap with protein binding sites, vesicle-sorting sites, structural sites, and novel small non-coding RNAs (sncRNAs). When applied in clinical cohorts, cfPeak identified cfRNA peaks in patients' plasma that enable cancer detection and are informative of cancer types and metastasis.

Our study fills the gap in the current small cfRNA-seq analysis at fragment-scale and builds a bridge to the scientific discovery in cfRNA fragmentomics. We demonstrate the significance of finding low abundant tissue-derived signals in small cfRNA and prove the feasibility for application in liquid biopsy.

Noncoding RNAs (ncRNAs) are a class of RNA molecules with little or no protein-coding potential. Emerging evidence indicates that ncRNAs are frequently dysregulated and play pivotal roles in the pathogenesis of pancreatic cancer. Their aberrant expression can arise from chromosomal abnormalities, dysregulated transcriptional control, and epigenetic modifications. ncRNAs function as protein scaffolds or molecular decoys to modulate interactions between proteins and other biomolecules, thereby regulating gene expression and contributing to pancreatic cancer progression. In this review, we summarize the mechanisms underlying ncRNA dysregulation in pancreatic cancer, emphasize the biological significance of ncRNA-protein interactions, and highlight their clinical relevance. A deeper understanding of ncRNA-protein interactions is essential to elucidate molecular mechanisms and advance translational research in pancreatic cancer.

In kidney transplantation, molecular diagnostics may be a valuable approach to improve the precision of the diagnosis. Using next-generation sequencing (NGS), we aimed to identify clinically relevant archetypes.

We conducted an Illumina bulk RNA sequencing on 770 kidney biopsies (540 kidney recipients) collected between 2006 and 2021 from 11 European centers. Differentially expressed genes were determined for 11 Banff lesions. An ElasticNet model was used for feature selection, and 4 machine learning classifiers were trained to predict the probability of presence of the lesions. NGS-based classifiers were used in an unsupervised archetypal analysis to different archetypes. The association of the archetypes with allograft survival was assessed using the iBox risk prediction score.

The ElasticNet feature selection reduced the number of the genes from a range of 859-10 830 to a range of 52-867 genes. NGS-based classifiers demonstrated robust performances (precision-recall area under the curves 0.708-0.980) in predicting the Banff lesions. Archetypal analysis revealed 8 distinct phenotypes, each characterized by distinct clinical, immunological, and histological features. Although the archetypes confirmed the well-defined Banff rejection phenotypes for T cell-mediated rejection and antibody-mediated rejection, equivocal histologic antibody-mediated rejection, and borderline diagnoses were reclassified into different archetypes based on their molecular signatures. The 8 NGS-based archetypes displayed distinct allograft survival profiles with incremental graft loss rates between archetypes, ranging from 90% to 56% rates 7 y after evaluation ( P < 0.0001).

Using molecular phenotyping, 8 archetypes were identified. These NGS-based archetypes might improve disease characterization, reclassify ambiguous Banff diagnoses, and enable patient-specific risk stratification.

Prostate cancer (PCa) is a leading cause of cancer-related morbidity and mortality in men worldwide. Despite advancements in diagnosis and treatment, challenges such as late-stage detection, therapeutic resistance, and the complexity of castration-resistant prostate cancer (CRPC) persist. Long non-coding RNAs (LncRNAs) play critical roles in PCa progression through epigenetic regulation, transcriptional and post-transcriptional modulation, and immune response regulation. This review highlights the molecular mechanisms by which LncRNAs influence PCa development, treatment resistance, and immune regulation, emphasizing their potential as biomarkers and therapeutic targets. We also discuss future research directions to advance precision medicine in PCa.

Cancer cells frequently upregulate ribosome production to support tumorigenesis. While small nucleolar RNAs (snoRNAs) are critical for ribosome biogenesis, the roles of other classes of noncoding RNAs in this process remain largely unknown. Here, we performed CRISPR interference (CRISPRi) screens to identify essential long noncoding RNAs (lncRNAs) in renal cell carcinoma (RCC) cells. This revealed that an alternatively spliced isoform of lncRNA colorectal neoplasia differentially expressed (CRNDE) containing an ultraconserved element (UCE), referred to as CRNDEUCE, is required for RCC cell proliferation. CRNDEUCE localizes to the nucleolus and promotes 60S ribosomal subunit biogenesis. The UCE of CRNDE functions as an unprocessed C/D box snoRNA that directly interacts with ribosomal RNA precursors. This facilitates delivery of eukaryotic initiation factor 6 (eIF6), a key 60S biogenesis factor, which binds to CRNDEUCE through a sequence element adjacent to the UCE. These findings highlight the functional versatility of snoRNA sequences and expand the known mechanisms through which noncoding RNAs orchestrate ribosome biogenesis.

Several studies have made it possible to envision a translational application of plasma DNA sequencing in cancer diagnosis and monitoring. However, the extremely low concentration of circulating tumour DNA (ctDNA) fragments among the total cell-free DNA (cfDNA) remains a formidable challenge to overcome and statistical models have yet to be improved enough to become of practical use. In this study, we set about appraising the predictive value of a variety of binary classification models based on cfDNA sequencing using fragmentation features extracted around transcription start sites (TSSs). We investigated (1) features summarising mapped fragment density around each TSS, (2) long non-coding RNA (lncRNA) genes versus coding genes and (3) selection criteria to generate gene classes to be assigned by the model. Given that, in healthy samples, most of the cfDNA comes from lymphomyeloid lineages, we could identify the model parametrisation with the best accuracy in those lineages using publicly available datasets of healthy patients' cfDNA. Our results show that (1) the way tissue-specific gene classes are defined matters more than what fragmentation features are included, and (2) in particular, lncRNAs are more tissue specific than coding genes and stand out in terms of both sensitivity and specificity in our results.

The skin, as the body's largest organ, functions as a vital barrier against environmental insults. Chronic exposure to ultraviolet (UV) radiation significantly contributes to premature aging, or photoaging, which leads to DNA damage and disrupts repair mechanisms. Exosomes, which are small extracellular vesicles, play a key role in cell-to-cell communication and might help mitigate the effects of photoaging by transporting bioactive molecules to skin cells. Long non-coding RNAs (lncRNAs) are increasingly recognized for their regulatory roles in the photoaging process, influencing stress responses and DNA repair; however, their involvement in exosomes in the context of skin aging is not yet well understood. In this study, we developed a photoaging model using SD rats subjected to UVA and UVB irradiation, which led to significant changes in the dermis such as increased dryness, wrinkles, pigmentation, and vascular alterations. Histological evaluations showed uneven thickening of the epidermis, degradation of collagen and elastic fibers, and cellular infiltration. Exosomes isolated from the dermal tissues exposed to UV radiation displayed altered size distributions. Transcriptomic analyses of the UV-treated rats identified 2,332 lncRNAs and 5,906 mRNAs that were differentially expressed, revealing significant involvement in pathways related to oxidative stress, apoptosis, and cellular stress responses. A cis-regulatory analysis identified 1,327 essential interactions between lncRNAs and mRNAs, highlighting their role in controlling inflammation and apoptosis. Importantly, both IL-1B and GADD45B levels were significantly increased in the exosomes and UV-challenged HaCaT cells, indicating their crucial roles in responding to UV-induced stress. This study highlights the significant role of exosomal lncRNAs in managing cellular reactions to UV-induced stress, impacting regulatory pathways associated with apoptosis, inflammation, and oxidative stress. These insights pave the way for the development of lncRNA-focused therapeutic approaches to address UV-induced skin damage.

Long-read sequencing (LRS) technologies have revolutionized transcriptomic research by enabling the comprehensive sequencing of full-length transcripts. Using these technologies, researchers have reported tens of thousands of novel transcripts, even in well-annotated genomes, while developing new algorithms and experimental approaches to handle the noisy data. The Long-read RNA-seq Genome Annotation Assessment Project community effort benchmarked LRS methods in transcriptomics and validated many novel, lowly expressed, often times sample-specific transcripts identified by long reads. These molecules represent deviations of the major transcriptional program that were overlooked by short-read sequencing methods but are now captured by the full-length, single-molecule approach. This Perspective discusses the challenges and opportunities associated with LRS' capacity to unravel this fraction of the transcriptome, in terms of both transcriptome biology and genome annotation. For transcriptome biology, we need to develop novel experimental and computational methods to effectively differentiate technology errors from rare but real molecules. For genome annotation, we must agree on the strategy to capture molecular variability while still defining reference annotations that are useful for the genomics community.

Mounting evidence indicates that long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis and progression of cancers. However, the functions and regulatory mechanisms of lncRNAs in prostate cancer (PCa) are still largely unknown. In this study, we found an lncRNA, PCa-associated transcript 71 (PRCAT71), highly expressed in metastatic and primary PCa compared to benign prostate tissues. Silencing PRCAT71 inhibited cancerous properties of PCa cells and androgen receptor (AR) signaling. Mechanistically, PRCAT71 acts as a scaffold to recruit K homology (KH)-type splicing regulatory protein (KHSRP) to AR messenger RNA (mRNA) and stabilize AR mRNA, leading to activated AR signaling. KHSRP plays a critical role in PCa progression. PRCAT71 is transcriptionally regulated by AR-driven enhancers, forming a positive regulatory loop between AR and PRCAT71 in PCa. Our study demonstrates a coordinated regulation of AR mRNA by lncRNA PRCAT71 and RNA binding protein KHSRP and provides insight that the PRCAT71-KHSRP-AR axis is a promising therapeutic target for treating PCa.

PANoptosis, a complex programmed cell death (PCD) pathway that includes apoptosis, pyroptosis and necroptosis, is significantly involved in the progression of cancers. Long noncoding RNAs (lncRNAs) play crucial roles in PCD. However, the predictive value of PANoptosis-related lncRNAs (PRlncRNAs) for colon adenocarcinoma (COAD) has not been established.

Gene expression data and clinical characteristics of patients with COAD were obtained from The Cancer Genome Atlas database. Differential expression analysis and Pearson correlation analysis were used to identify PRlncRNAs. In addition to least absolute shrinkage and selection operator, univariate and multivariate Cox regression analyses were employed to obtain PRlncRNAs for constructing a risk signature. Patients with COAD in the training set, testing set and entire set were stratified into high- and low-risk groups for further comparison of survival prognosis, using the median risk score as the cut-off point. Time-dependent receiver operating characteristic curves, a nomogram and multivariate Cox regression analysis were conducted to validate the risk signature in the testing set and the entire set. In addition, critical pathways, immune infiltration cells, immune checkpoint-related genes, Tumor Immune Dysfunction and Exclusion (TIDE) scores and antitumour drugs were compared between the two risk groups in the entire set. Correlations between ferroptosis, cuproptosis, disulfidptosis and the PRlncRNA risk score were evaluated. Finally, a competitive endogenous RNA (ceRNA) network was established, and enrichment analysis of the predicted mRNAs was performed using Gene Ontology (GO) analysis. The Kaplan-Meier plotter database was used as an external database to confirm the accuracy of the risk signature in predicting patient prognosis. Additionally, small interfering RNA (siRNA), a cell counting kit- 8 assay, a cell colony formation assay, quantitative polymerase chain reaction (qPCR) and an apoptosis assay were further employed to investigate the roles of AP003555.1 in colon cancer.

A risk signature comprising four PRlncRNAs (LINC01133, FOXD3-AS1, AP001066.1, and AP003555.1) was developed to predict the prognosis of patients with COAD. Kaplan‒Meier curves demonstrated significant differences in prognosis between the high- and low-risk groups across the three sets. Multivariate Cox regression analysis confirmed that the risk signature was an independent prognostic factor across the three sets. A nomogram, receiver operating characteristic curves and calibration curves indicated strong confidence in the risk signature. Using the CIBERSORT algorithm and gene set enrichment analysis, variations in infiltrating immune cells and immune processes were observed between the two risk groups. Furthermore, TIDE algorithm suggested that the high-risk group exhibited a lower risk of immunotherapy escape and better immunotherapy outcomes than the low-risk group. Distinct responses to various antitumour drugs were observed between the two risk groups. Additionally, we constructed a ceRNA network based on PRlncRNAs, and GO enrichment analysis of the predicted mRNAs revealed different functions. In addition, the results of the Kaplan‒Meier plotter database revealed that patients who exhibited high levels of LINC01133 and FOXD3-AS1 experienced significantly shorter overall survival than those with low levels of these lncRNAs. Specifically, in terms of functionality, AP003555.1 was found to be highly expressed in colon cancer tissue and promoted viability and proliferation while suppressing the apoptosis of colon cancer cells.

We identified a novel risk signature consisting of four PRlncRNAs, which is an independent prognostic indicator for patients with COAD. This PRlncRNA risk signature is potentially relevant for immunotherapy and could serve as a therapeutic target for COAD.

Hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular adaptation to hypoxia, drives colorectal cancer (CRC) progression by fueling angiogenesis, metastasis, and therapy resistance. Emerging evidence delineates intricate crosstalk between non-coding RNAs (ncRNAs)-including microRNAs, long non-coding RNAs, and circular RNAs-and HIF-1α, forming bidirectional regulatory networks that orchestrate CRC pathogenesis. By interacting with HIF-1α, these non-coding RNAs contribute to the orchestration of the aggressive hypoxic tumor microenvironment. Recent studies have evaluated the clinical potential of lncRNAs and miRNAs in the realms of non-invasive liquid biopsies and RNA-targeted therapies. This review offers a comprehensive synthesis of recent investigations into the mechanisms by which lncRNAs and miRNAs interact with HIF-1α to modulate CRC progression. Additionally, we further explore the clinical implications of ncRNA/HIF-1α crosstalk, emphasizing their potential as diagnostic biomarkers and therapeutic targets, while also spotlighting intriguing and promising areas of ncRNA research. Methods: In this study, our search strategy employed in databases such as PubMed, Web of Science, and EMBASE is as follows: we will specify search terms, including combinations of "non-coding RNA", "HIF-1α", and "colorectal cancer", along with a date range for the literature search (for example, from 2000 to 2025) to capture the most relevant and up-to-date research.

Long noncoding RNAs (lncRNAs) play critical roles in the initiation and progression of breast cancer. However, the specific mechanisms and biological functions of lncRNAs in breast cancer remain incompletely understood. Bioinformatics analysis identifies a novel lncRNA, CD2BP2-DT, that is overexpressed in breast cancer and correlates with adverse clinicopathological features and poor overall survival. Both in vivo and in vitro experiments demonstrate that CD2BP2-DT promotes proliferation of breast cancer cells. Mechanistically, NAT10 mediates the N4-acetylcytidine (ac4C) modification of CD2BP2-DT, enhancing its RNA stability and expression. More importantly, CD2BP2-DT enhances the stability of CDK1 mRNA by mediating YBX1 phase separation, thereby promoting the proliferation of breast cancer cells. In conclusion, the lncRNA CD2BP2-DT is identified as a crucial driver of breast cancer cell proliferation through the YBX1/CDK1 axis, highlighting its potential as a promising biomarker and therapeutic target for breast cancer.

Non-coding RNAs (ncRNAs) have gained significant attention in recent years due to advancements in biotechnology, particularly high-throughput total RNA sequencing. These developments have led to new understandings of non-coding biology, revealing that approximately 80% of non-coding regions in the genome possesses biochemical functionality. Among ncRNAs, circular RNAs (circRNAs), first identified in 1976, have emerged as a prominent research field. CircRNAs are abundant in most human cell types, evolutionary conserved, highly stable, and formed by back-splicing events which generate covalently closed ends. Notably, circRNAs exhibit high expression levels in neural tissue and perform diverse biochemical functions, including acting as molecular sponges for microRNAs, interacting with RNA-binding proteins to regulate their availability and activity, modulating transcription and splicing, and even translating into functional peptides in some cases. Recent advancements in computational and experimental methods have enhanced our ability to identify and validate circRNAs, providing valuable insights into their biological roles. This review focuses on recent developments in circRNA research as they related to neuropsychiatric and neurodegenerative conditions. We also explore their potential applications in clinical diagnostics, therapeutics, and future research directions. CircRNAs remain a relatively underexplored area of non-coding biology, particularly in the context of neurological disorders. However, emerging evidence supports their role as critical players in the etiology and molecular mechanisms of conditions such as schizophrenia, bipolar disorder, major depressive disorder, Alzheimer's disease, and Parkinson's disease. These findings suggest that circRNAs may provide a novel framework contributing to the molecular dysfunctions underpinning these complex neurological conditions.

The oriental fruit fly, Bactrocera dorsalis (Hendel) is an invasive pest threatening global fruit industries. Field populations of B. dorsalis exhibit complex insecticide resistance, hindering pest control efforts and exacerbating damage. Long non-coding RNAs (lncRNAs) are critical regulators of multiple bioprocess in insects, including insecticide resistance, and have potentials as novel target for pest management. Here, the candidate lncRNAs associated with malathion resistance in B. dorsalis were identified through RNA-seq. One of the isoforms of lnc37707, designated as lnc37707.10, was significantly enriched in the detoxification tissues of malathion-resistant (MR) strain. A specific fragment of lnc37707.10 (sflnc37707) was strongly associated with malathion resistance, and silencing sflnc37707 increased the susceptibility, whereas overexpressing it decreased susceptibility to malathion. Silencing sflnc37707 resulted in the down-regulation of 248 genes, but none of them included the four adjacent genes as its potential target. Instead, pathway analysis revealed significant enrichment of down-regulated genes involved in drug and xenobiotics metabolism, including P450s and GSTs. Bioinformatic analysis suggested a potential regulatory role of miRNA in the function of lnc37707. Further combining silence or overexpression sflnc37707 with miRNA mimic treatment identified that BdGSTd10 (an important gene involved in malathion resistance) and miR-1000 was strongly linked to lnc37707.10. Finally, a ceRNA (competing endogenous RNA) regulatory axis was proposed, where lnc37707.10 might indirectly modulate BdGSTd10 by sponging miR-1000 to regulate the malathion resistance in B. dorsalis. These findings provide a new insight into insecticide resistance and a potential lncRNA target for the sustainable pest management.

Ankylosing spondylitis (AS) is recognized as a long-term inflammatory disorder that leads to inflammation in the spine and joints, alongside abnormal bone growth. In previous studies, we reported that mesenchymal stem cells (MSCs) derived from individuals with AS demonstrated a remarkable inhibition in the formation of osteoclasts compared to those obtained from healthy donors. The mechanism through which MSCs from AS patients achieve this inhibition remains unclear.

To investigate the potential underlying mechanism by which MSCs from individuals with ankylosing spondylitis (AS-MSCs) inhibit osteoclastogenesis.

We analysed fat mass and obesity-associated (FTO) protein levels in AS-MSCs and MSCs from healthy donors and investigated the effects and mechanism by which FTO in MSCs inhibits osteoclastogenesis by coculturing and measuring the levels of tartrate-resistant acid phosphatase, nuclear factor of activated T cells 1 and cathepsin K.

We found that FTO, an enzyme responsible for removing methyl groups from RNA, was more abundantly expressed in MSCs from AS patients than in those from healthy donors. Reducing FTO levels was shown to diminish the capacity of MSCs to inhibit osteoclast development. Further experimental results revealed that FTO affects the stability of the long non-coding RNA activated by DNA damage (NORAD) by altering its N6-methyladenosine methylation status. Deactivating NORAD in MSCs significantly increased osteoclast formation by affecting miR-4284, which could regulate the MSC-mediated inhibition of osteoclastogenesis reported in our previous research.

This study revealed elevated FTO levels in AS-MSCs and found that FTO regulated the ability of AS-MSCs to inhibit osteoclast formation through the long noncoding RNA NORAD/miR-4284 axis.

This study examines the critical role of non-coding RNAs (ncRNAs) in regulating epithelial-mesenchymal transition (EMT) in breast cancer, a prevalent malignancy with significant metastatic potential. EMT, wherein cancer cells acquire mesenchymal traits, is fundamental to metastasis. ncRNAs-such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)-modulate EMT by influencing gene expression and signaling pathways, affecting cancer cell migration and invasion. This review consolidates recent findings on ncRNA-mediated EMT regulation and explores their diagnostic and therapeutic potential. Specifically, miRNAs inhibit EMT-related transcription factors, while lncRNAs and circRNAs regulate gene expression through interactions with miRNAs, impacting EMT progression. Given the influence of ncRNAs on metastasis and therapeutic resistance, advancing ncRNA-based biomarkers and treatments holds promise for improving breast cancer outcomes.

Unlike protein-coding genes, most human long noncoding RNAs (lncRNAs) lack conservation based on their sequences, posing a challenge for investigating their role in a pathophysiological context for clinical translation. This study explores the hypothesis that nonconserved lncRNAs in human and mouse livers may share similar metabolic functions, giving rise to functionally conserved lncRNA metabolic regulators (fcLMRs).

We developed a sequence-independent strategy to select putative fcLMRs and performed extensive analysis to determine the functional similarities of putative human and mouse (h/m)LMR pairs.

We found that several pairs of putative fcLMRs share similar functions in regulating gene expression. We further demonstrated that a pair of fcLMRs, h/mLMR1, robustly regulated triglyceride levels by modulating the expression of a similar set of lipogenic genes. Mechanistically, h/mLMR1 binds to poly(A)-binding protein cytoplasmic 1 (PABPC1), a regulator of protein translation, via short motifs on either lncRNA with divergent sequences but similar structures. This interaction inhibits protein translation, activating an amino acid- mechanistic target of rapamycin-sterol regulatory element-binding transcription factor 1 axis to regulate lipogenic gene expression. Intriguingly, PABPC1-binding motifs on each lncRNA fully rescued the functions of their corresponding LMRs in the opposite species. Given the elevated expression of h/mLMR1 in humans and mice with hepatic steatosis, the PABPC1-binding motif on hLMR1 emerges as a potential nonconserved human drug target whose functions can be fully validated in a physiologically relevant setting before clinical studies.

Our study supports that fcLMRs represent a novel and prevalent biological phenomenon and that deep phenotyping of genetic mLMR mouse models constitutes a powerful approach to understand the pathophysiological role of lncRNAs in the human liver.

Gliomas, a type of malignant tumor, are marked by a short survival period and an unfavorable prognosis. Disulfide stress, which arises from an overabundance of intracellular cystine, can initiate disulfidoptosis, an emerging form of cell death. The link between gliomas and disulfidoptosis has not been extensively explored. This study breaks new ground by investigating the correlation between glioma prognosis and lncRNAs associated with disulfidoptosis, with the aim of improving glioma treatment strategies.

We analyzed 10 long non-coding RNAs (lncRNAs) co-expressed with disulfidoptosis genes, retrieved clinical information and gene expression profiles from glioma and normal groups in the TCGA database, and developed a prognostic model for lncRNAs based on this data. The receiver operating characteristic curve (ROC) was used to evaluate and validate the model's reliability. Furthermore, the Kaplan-Meier survival curve was employed to assess the disparity in overall survival (OS) among patients with varying risk scores. We also examined the tumor microenvironment (TME), immune cell infiltration, immune-related functions, tumor mutational burden (TMB), and OncoPredict in samples with differing risk scores. To confirm the expression variations of genes associated with prognostic models in cell lines, quantitative polymerase chain reaction (qPCR) was employed.

Eleven long non-coding RNAs (lncRNAs) were identified for constructing prognostic models by analyzing lncRNAs associated with disulfidoptosis genes using Cox regression and LASSO regression analyses. The study's findings indicate that these 11 key lncRNAs serve as independent predictors of overall survival (OS) in glioma patients. Moreover, the frequency with which patients of varying risk scores opt for immune checkpoint blockade (ICB) therapy and chemotherapy not only differs but also their responses to these treatments are significantly distinct, suggesting that the risk score could be a predictive factor for treatment response.

This research sheds light on the characteristics of disulfidoptosis in glioma, revealing that patterns of disulfidoptosis in patients can be effectively assessed using a risk score. Consequently, the judicious application of this prognostic model can significantly inform clinical treatment strategies and precision medicine for glioma, potentially improving patient outcomes.

Glioblastoma multiforme (GBM) is characterized by substantial heterogeneity and limited therapeutic options. As molecular approaches to central nervous system tumors have gained prominence, this study examined the roles of three genes, TWIST2, GATA3, and HES5, known to be involved in oncogenesis, developmental processes, and maintenance of cancer stem cell properties, which have not yet been extensively studied in GBM. This study is the first to present gene expression data for TWIST2, GATA3, and HES5 specifically within the context of GBM patient survival.

Gene expression data for TWIST2, GATA3, and HES5 were collected from GBM and normal brain tissues using datasets from The Cancer Genome Atlas via the Genomic Data Commons portal and the Genotype-Tissue Expression database. These data were rigorously analyzed using in silico methods.

All three genes were significantly more expressed in GBM tissues than in normal tissues. TWIST2 and GATA3 were linked to lower survival rates in GBM patients. Interestingly, higher HES5 levels were associated with better survival rates, suggesting a complex role that needs more investigation.

This study shows that TWIST2, GATA3, and HES5 could help predict outcomes in GBM patients. Our multigene model offers a better understanding of GBM and points to new treatment options, bringing hope for improved therapies and patient outcomes. This research advances our knowledge of GBM and highlights the potential of molecular diagnostics in oncology.

Chemoresistance remains a major hurdle in ovarian cancer (OC) treatment, as many patients eventually develop resistance to platinum-based chemotherapy and/or PARP inhibitors (PARPi).

We performed transcriptome-wide analysis by RNA sequencing (RNA-seq) data of platinum-resistant and -sensitive OC tissues. We demonstrated the role of LINC02776 in platinum resistance in OC cells, mice models and patient-derived organoid (PDO) models.

We identify the long noncoding RNA LINC02776 as a critical factor of platinum resistance. Elevated expression of LINC02776 is observed in platinum-resistant OC and serves as an independent prognostic factor for OC patients. Functionally, silencing LINC02776 reduces proliferation and DNA damage repair in OC cells, thereby enhancing sensitivity to platinum and PARPi in both xenograft mouse models and patient-derived organoid (PDO) models with acquired chemoresistance. Mechanistically, LINC02776 binds to the catalytic domain of poly (ADP-ribose) polymerase 1 (PARP1), promoting PARP1-dependent polyADP-ribosylation (PARylation) and facilitating homologous recombination (HR) restoration. Additionally, high HIF-1α expression in platinum-resistant tissues further stimulates LINC02776 transcription.

Our findings suggest that targeting LINC02776 represents a promising therapeutic strategy for OC patients who have developed resistance to platinum or PARPi.

LINC02776 promotes OC cell proliferation by regulating DNA damage and apoptosis signaling pathways. LINC02776 binds PARP1 to promote DNA damage-triggered PARylation in OC cells. LINC02776 mediates cisplatin and olaparib resistance in OC cells by enhancing PARP1-mediated PARylation activity and regulating the PARP1-mediated HR pathway. The high expression of LINC02776 is induced by HIF-1α in platinum-resistant OC cells and tissues.

The systematic identification and functional characterization of noncanonical translation products, such as novel peptides, will facilitate the understanding of the human genome and provide new insights into cell biology. Here, we constructed a high-coverage peptide sequencing reference library with 11,668,944 open reading frames and employed an ultrafiltration tandem mass spectrometry assay to identify novel peptides. Through these methods, we discovered 8945 previously unannotated peptides from normal gastric tissues, gastric cancer tissues and cell lines, nearly half of which were derived from noncoding RNAs. Moreover, our CRISPR screening revealed that 1161 peptides are involved in tumor cell proliferation. The presence and physiological function of a subset of these peptides, selected based on screening scores, amino acid length, and various indicators, were verified through Flag-knockin and multiple other methods. To further characterize the potential regulatory mechanisms involved, we constructed a framework based on artificial intelligence structure prediction and peptide‒protein interaction network analysis for the top 100 candidates and revealed that these cancer-related peptides have diverse subcellular locations and participate in organelle-specific processes. Further investigation verified the interacting partners of pep1-nc-OLMALINC, pep5-nc-TRHDE-AS1, pep-nc-ZNF436-AS1 and pep2-nc-AC027045.3, and the functions of these peptides in mitochondrial complex assembly, energy metabolism, and cholesterol metabolism, respectively. We showed that pep5-nc-TRHDE-AS1 and pep2-nc-AC027045.3 had substantial impacts on tumor growth in xenograft models. Furthermore, the dysregulation of these four peptides is closely correlated with clinical prognosis. Taken together, our study provides a comprehensive characterization of the noncanonical proteome, and highlights critical roles of these previously unannotated peptides in cancer biology.

Breast cancer represents the most common type of cancer in females worldwide. The survival rates for breast cancer patients have been increasing since 1990. However, in 2023 breast cancer is still the second most common cause of malignancy-associated death in women. One decisive reason is the increase of treatment resistance and low therapy response. Therefore, new therapy targets and predictive markers for the response to treatment are needed. The present study analyzed the potential effects triggered by different breast cancer treatments on the transcriptional expression of 12 pre-selected long non-coding (lnc) RNAs and the proliferation markers Cyclin D1 and Ki-67 in six different breast cancer cell lines (BT-474, MDA-MB-231, BT-20, T-47D, SKBR-3 and MCF-7). The results revealed that lncRNA cytoskeleton regulator RNA may be an appropriate biomarker for the response to treatment with both epirubicin and gemcitabine (P<0.001). NF-ĸB interacting lnc RNA may be a marker for therapy response (P<0.001), while HOX transcript antisense RNA overexpression suggested resistance to treatment (P<0.001) with epirubicin. The transcriptional expression of lncRNA BC4 increased during treatment with epirubicin and gemcitabine, which indicated therapy response. Overall, the present data suggested that the aforementioned lncRNAs have a promising potential as biomarkers to detect early therapy response or resistance in and therefore should be analyzed in more detail.

Multi-omics has helped elucidate the gene expression patterns and genomic variations closely associated with economically significant traits in geese. Despite the substantial genomic data generated through extensive goose studies, a unified platform for integrating these datasets is lacking. To address this gap, we introduced the Goose Multi-omics Database (GMD), which is accessible at http://goosedb.com/. The GMD is a comprehensive resource enabling streamlined search, analysis, and visualization of genetic information through a unified interface, providing insights into phenotypic traits, gene sequences, structures, expression profiles, genomic variations, gene families, homology, and collinearity. Equipped with robust analytical tools such as GBrowse and BLAST, the GMD facilitates rapid access to target gene information, significantly enhancing the efficiency and productivity of genomic research. By serving as a versatile and intuitive online repository, the GMD offers transformative potential for advancing goose biology, fostering multi-omics investigations, and integrating cutting-edge methodologies such as deep learning to accelerate discoveries in goose genomics.

The field of ribonucleic acid (RNA) biology has revealed an array of noncoding RNA species, particularly long noncoding RNAs (lncRNAs), which play crucial roles in liver disease pathogenesis. This review explores the diverse functions of lncRNAs in liver pathology, including metabolic-associated steatotic liver disease, hepatocellular carcinoma, alcohol-related liver disease, and cholangiopathies such as primary sclerosing cholangitis and cholangiocarcinoma. We highlight key lncRNAs that regulate lipid metabolism, inflammation, fibrosis, and oncogenesis in the liver, demonstrating their diagnostic and therapeutic potential. Emerging RNA-based therapies, such as mRNA therapy, RNA interference, and antisense oligonucleotides, offer approaches to modulate lncRNA activity and address liver disease at a molecular level. Advances in sequencing technologies and bioinformatics pipelines are simultaneously enabling the identification and functional characterization of novel lncRNAs, driving innovation in personalized medicine. In conclusion, this review highlights the potential of lncRNAs as biomarkers and therapeutic targets in liver disease and emphasizes the need for further research into their regulatory mechanisms and clinical applications.

Thousands of short open reading frames (sORFs) are translated outside of annotated coding sequences. Recent studies have pioneered searching for sORF-encoded microproteins in mass spectrometry (MS)-based proteomics and peptidomics datasets. Here, we assessed literature-reported MS-based identifications of unannotated human proteins. We find that studies vary by three orders of magnitude in the number of unannotated proteins they report. Of nearly 10,000 reported sORF-encoded peptides, 96% were unique to a single study, and 12% mapped to annotated proteins or proteoforms. Manual curation of a benchmark dataset of 406 manually evaluated spectra from 204 sORF-encoded proteins revealed large variation in peptide-spectrum match (PSM) quality between studies, with immunopeptidomics studies generally reporting higher quality PSMs than conventional enzymatic digests of whole cell lysates. We estimate that 65% of predicted sORF-encoded protein detections in immunopeptidomics studies were supported by high-quality PSMs versus 7.8% in non-immunopeptidomics datasets. Our work stresses the need for standardized protocols and analysis workflows to guide future advancements in microprotein detection by MS towards uncovering how many human microproteins exist.

Skin cutaneous melanoma (SKCM) is a cancer with serious global impact. Long non-coding RNA was previously found to be associated with tumor prognosis. This research focuses on long intergenic non-protein coding (LINC) RNAs, and correlated protein-coding genes (PCGs), to explore their diagnostic and prognostic value, function and mechanism. Gene expression data was obtained from TCGA and Oncomine for analysis; in total there were 458 cases included in this study. LIN00518 and the 10 most highly correlated PCGs were selected to determine the diagnostic and prognostic value. We undertook bioinformatic analysis with LINC00518 and the prognostic-related PCGs in order to explore their molecular mechanism. The Connectivity Map was carried out for pharmacological target prediction and drug selection. Among the top 10 correlated PCGs, trafficking kinesin protein 2 (TRAK2), epilepsy of progressive myoclonus type 2 gene A (EPM2A) and melanocyte inducing transcription factor (MITF) had significant diagnostic value (all AUC > 0.7, P < 0.05). LINC00518, ras association domain family member 3 (RASSF3), cdk5 and Abl enzyme substrate 1 (CABLES1), kazrin, periplakin interacting protein (KAZN), EF-hand calcium binding domain 5 (EFCAB5) and MITF were significantly associated with prognosis (all adjusted P < 0.05). LINC00518 was associated with cell cycle process, melanogenesis, MAPK signaling pathway, cell division and DNA repair(all P < 0.05). Pharmacological targets analysis suggested results acquired eight potential target drugs. Up-regulation of LINC00518 is significantly associated with poor prognosis. TRAK2, EPM2A and MITF had diagnostic significance. RASSF3, CABLES1, KAZN, EFCAB5 and MITF had prognostic significance. This study provided novel biomarkers for SKCM.

Recent years have seen an increase in our understanding of lncRNA and their role in various disease states. lncRNA molecules have been shown to contribute to carcinogenesis and influence the various cancer hallmarks and signalling pathways. It is pertinent to understand the specific contributions and mechanisms of action of these molecules in various cancers. This review provides an overview of the various lncRNA entities that influence and regulate the gynaecological cancers, namely, cervical, breast, ovarian and uterine cancers. The review curates a list of the key players and their effect on cellular processes. lncRNA molecules show immense potential to be used as diagnostic and prognostic indicators and in therapeutic strategies. Several phytochemicals, small molecules, RNA-based regulators, oligos and gene editing tools show promise as a therapeutic strategy. While this review highlights the promising developments in this field, it also underscores the necessity for further research to delineate the complex role of lncRNAs in cancer.

Long non-coding RNAs (lncRNAs) are a class of non-coding RNA molecules with transcripts longer than 200 bp, which were initially thought to be noise from genomic transcription without biological function. However, since the discovery of H19 in 1980 and Xist in 1990, increasing evidence has shown that lncRNAs regulate gene expression at epigenetic, transcriptional, and post-transcriptional levels through specific regulatory actions and are involved in the development of cancer and other diseases. Despite many lncRNAs being expressed at lower levels than those of protein-coding genes with less sequence conservation across species, lncRNAs have become an intense area of RNA research. They exert diverse biological functions such as inducing chromatin remodeling, recruiting transcriptional machinery, acting as competitive endogenous RNAs for microRNAs, and modulating protein-protein interactions. Epithelial-mesenchymal transition (EMT) is a developmental process, associated with embryonic development, wound healing, and cancer progression. In the context of oncogenesis, the EMT program is transiently activated and confers migratory/invasive and cancer stem cell (CSC) properties to tumor cells, which are crucial for malignant progression, metastasis, and therapeutic resistance. Accumulating evidence has revealed that lncRNAs play crucial roles in the regulation of tumor epithelial/mesenchymal plasticity (EMP) and cancer stemness. Here, we summarize the emerging roles and molecular mechanisms of lncRNAs in regulating tumor cell EMP and their effects on tumor initiation and progression through regulation of CSCs. We also discuss the potential of lncRNAs as diagnostic and prognostic biomarkers and therapeutic targets.