Non-coding RNAs Research Articles

MYLK-AS1 Enhances Glutamine Metabolism to Promote EGFR Inhibitor Resistance in Non-Small Cell Lung Cancer.

Acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) limits the efficacy of molecular targeted therapy in non-small cell lung cancer (NSCLC). Metabolic reprogramming is a hallmark of lung cancer that could contribute to TKI resistance. Through systematic screening and verification, we identified a role for the long noncoding RNA (lncRNA) MYLK-AS1 supporting acquired TKI resistance in lung cancer. Elevated expression of MYLK-AS1 correlated with TKI resistance in NSCLC patient samples and cell lines. c-Myc mediated transcriptional activation of MYLK-AS1, and m6A modification promoted post transcriptional upregulation. Mechanistically, MYLK-AS1 bound and directly drove phase separation of interleukin enhancer binding factor 3 (ILF3), thus interacting with the 3'UTR of glutamate dehydrogenase 1 (GLUD1) to post-transcriptionally promote its mRNA stability. MYLK-AS1-mediated GLUD1 upregulation accelerated mitochondrial glutamine catabolism, promoting TKI resistance. Inhibition of GLUD1 with the small-molecule inhibitor R162 in TKI resistant models suppressed cell proliferation in vitro and tumor growth in vivo. Moreover, knockdown of MYLK-AS1 also enhanced drug sensitivity in TKI resistant patient-derived xenograft models, suggesting its therapeutic potential. Collectively, these findings offer insights into the regulation of TKI resistance from the perspective of phase separation and metabolism and highlight targeting the MYLK-AS1/ILF3/GLUD1 axis as a potential strategy for improving the efficacy of EGFR TKIs in NSCLC.

NcRNAs as Key Regulators in Gastric Cancer: From Molecular Subtyping to Therapeutic Targets.

Gastric cancer (GC) poses a major global health challenge, underscoring the need for advanced diagnostic and therapeutic approaches. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators in GC, with their dysregulated expression driving key processes such as tumorigenesis, metastasis, immune evasion, and chemoresistance. The functional diversity of ncRNAs across different GC molecular subtypes highlights their potential as biomarkers for improved subtype classification and patient stratification. Beyond their diagnostic value, ncRNAs demonstrate critical regulatory functions in tumor biology, establishing these RNA molecules as promising targets for therapeutic development. Strategies based on RNA hold considerable promise for addressing critical challenges such as immune escape and drug resistance by modulating key signaling pathways. These approaches can enhance immune responses, reprogram the tumor microenvironment, and reverse resistance mechanisms that compromise treatment efficacy, thereby improving clinical outcomes. Although ncRNAs represent a promising frontier in GC precision medicine, further research is required to fully harness their clinical potential.

Interplay between NETosis and the lncRNA-microRNA regulatory axis in the immunopathogenesis of cancer.

Neutrophil extracellular traps (NETs), web-like complex structures secreted by neutrophils, have emerged as key players in the modulation of immune responses and the immunopathogenesis of immune disorders. Initially described for their antimicrobial function, NETs now play a part in the fundamental processes of cancer biology, including cancer initiation, metastatic dissemination, and immune evasion strategies. NETs hijack anti-tumor immunity by entrapping circulating cancer cells, fostering the growth of tumors, and reorganizing the tumor microenvironment such that it is pro-malignancy. Emerging evidence emphasizes the role of NETosis coupled with non-coding RNAs-long non-coding RNAs (lncRNAs) and microRNAs (miRNAs)-as key regulators of gene expression and controllers of processes vital for cancer growth, such as immune response and programmed cell death processes like apoptosis, necroptosis, pyroptosis, and ferroptosis. Aberrantly expressed non-coding RNAs have been attributed to immune dysregulation and excessive NET production, promoting tumor growth. NETs are also associated with a myriad of pathological conditions, such as autoimmune disorders, cystic fibrosis, sepsis, and thrombotic disorders. New therapeutic approaches-such as DNase therapy and PAD4 inhibitors-target NET production and their degradation to modify immune function and the efficiency of immunotherapies. Further clarification of the intricate interactions of NETosis, lncRNAs, and miRNAs has the potential to establish new strategies for the suppression of the growth of tumors and preventing immune evasion. This review seeks to elucidate the interactions between NETosis and the regulatory networks involving non-coding RNAs that significantly contribute to the immunopathogenesis of cancer.

Analysis and ceRNA Network Construction of Differentially Expressed lncRNAs and mRNAs in Human Osteoarthritis Cartilage.

This study aimed to identify differentially expressed long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in damaged cartilage (DC) and un-damaged cartilage (UDC) in human osteoarthritis (OA), exploring their roles in disease progression through bioinformatics analysis and ceRNA network construction. Cartilage samples from 5 OA patients undergoing total knee arthroplasty were analyzed. RNA sequencing was used to detect the expression of lncRNAs and mRNAs in DC and UDC samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to investigate biological processes. A ceRNA network was constructed, and differentially expressed RNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). In the damaged cartilage (DC) samples, 5 lncRNAs were significantly upregulated, and 15 were significantly downregulated, while 8 mRNAs were upregulated, and 8 were downregulated. The differential expression of lncRNAs, including LINC01411, AL596087.2, PCDH20, LRFN2, and AL583785.1, was confirmed using qRT-PCR, with p-values for all results showing statistical significance (p < 0.05). GO/KEGG enrichment analysis revealed key pathways such as Ras, PI3K-Akt, and MAPK that were significantly involved in OA pathogenesis. The ceRNA network construction highlighted crucial miRNA interactions, identifying potential regulators of cartilage-related biological processes. Differentially expressed lncRNAs and mRNAs are involved in critical signaling pathways in OA cartilage, suggesting their potential as biomarkers or therapeutic targets for OA treatment. Further functional studies are needed to fully elucidate their roles in OA pathogenesis.

LncRNA SCARNA8 promotes atherosclerotic plaque instability by inhibiting macrophage efferocytosis

ABSTRACT In recent years, findings suggest that long noncoding RNAs (lncRNAs) are closely related to the development of atherosclerosis (AS), but there is a lack of studies on the involvement of lncRNA-regulated cytosolic burial in the regulation of AS. In this study, we investigated the mechanism by which lncRNA SCARNA8 affects macrophage cell burial to regulate AS. The cytosolic burial-associated target gene regulated by lncRNA SCARNA8 was PPARG. LncRNA SCARNA8 was increased in the carotid unstable plaque group, whereas PPARG was decreased. Ox-LDL led to the up-regulation of lncRNA SCARNA8 expression and apoptosis in Raw264.7 cells in a time-, concentration-dependent manner. Knockdown of lncRNA SCARNA8 upregulated PPARG and reduced apoptosis in Raw264.7 cells. In addition, knockdown of lncRNA SCARNA8 improved the stability of atherosclerotic plaques by promoting cellular burial of Raw264.7 cells. LncRNA SCARNA8 is a key regulator of plaque vulnerability, and targeting lncRNA SCARNA8 May provide a novel means for the prevention and treatment of AS.

LncRNA MEG3 promotes pyroptosis via miR-145-5p/TLR4/NLRP3 axis and aggravates cerebral ischemia-reperfusion injury

Long noncoding RNA (lncRNA) MEG3 has been considered as a novel target for alleviating the brain tissue damage during cerebral ischemia-reperfusion injury (CIRI). Numerous studies have reported that pyroptosis is involved in the pathogenesis of CIRI. This study focused on whether MEG3 modulates CIRI via pyroptosis and its underlying mechanism. The middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model and the oxygen glucose deprivation/reoxygenation (OGD/R) cell model were established. si-MEG3 and miR-145-5p inhibitor were transfected to inhibit MEG3 and miR-145-5p, respectively. As a TLR4 inhibitor, Resatorvid inhibits the TLR4 signaling pathway. TTC and TUNEL staining were used for infarction volume and cell death detection. The differential expression of MGE3, miR-145-5p, TLR4, NLRP3, Caspase-1, IL-1β, and IL-18 was determined using real-time PCR and western blot. The interaction between MEG3 and miR-145-5p, as well as between miR-145-5p and TLR4 was confirmed by the dual-luciferase reporter assay. This study confirmed that the elevated expression of MEG3 during CIRI, and it contributes to pyroptosis by regulating miR-145-5p/TLR4 axis. The knockdown of MEG3 reduced the expression of TLR4, NLRP3, Caspase-1, IL-1β, and IL-18, thereby preventing pyroptosis. Inhibition of miR-145-5p reversed the effect of MEG3 knockdown and promoted pyroptosis. Resatorvid, the inhibitor of TLR4, counteracted the effect of miR-145-5p inhibitor and suppressed pyroptosis. Our findings reveal that MEG3 promotes pyroptosis via miR-145-5p/TLR4/NLRP3 axis and aggravates CIRI, suggesting a potential therapeutic target for ischemic stroke.Graphical abstract

Epigenetic dynamics and molecular mechanisms in oncogenesis, tumor progression, and therapy resistance.

Cancer progression is governed by a dynamic interplay of genetic, epigenetic, and molecular mechanisms that regulate tumor initiation, growth, metastasis, and therapy resistance. This review highlights key molecular pathways involved in oncogenesis, focusing on genetic alterations (mutations, amplifications, and translocations) in oncogenes (RAS and MYC) and tumor suppressor genes (TP53 and PTEN). Additionally, genomic instability, resulting from defective DNA repair mechanisms like mismatch repair and homologous recombination (HR), is identified as a critical factor contributing to tumor heterogeneity and clonal evolution. Epigenetic modifications, including DNA methylation, histone acetylation, and non-coding RNA regulation, further remodel chromatin structure and modulate gene expression, influencing tumor initiation, growth, metastasis, and response to treatment. Post-translational modifications, such as the attachment of a Small Ubiquitin-like Modifier (SUMO) to a target protein and ubiquitination, further influence autophagy, apoptosis, and cellular plasticity, enabling cancer cells to survive therapeutic stress. Cutting-edge technologies such as CRISPR-Cas9-mediated epigenome editing and single-cell RNA sequencing have opened new doors to understanding cellular diversity and regulatory networks in cancer. The review further examines the tumor microenvironment, including stromal remodeling, immune evasion, and hypoxia-driven signaling pathways, which are critical modulators of tumor progression and drug resistance to treatment. By integrating molecular, genetic, and epigenetic perspectives, this study underscores the crucial need for innovative, targeted therapeutic approaches to address the complexity and adaptability of cancer, thereby paving the way for more effective treatments.

Exploring the Role of Long Non-Coding RNAs in Mediating Cisplatin Resistance in Colorectal Cancer.

Colorectal cancer (CRC) usually begins as adenomatous polyps in the colorectal or rectal epithelial cells. Currently, there are no reliable biomarkers for early CRC screening or prognostic prediction, leading to late-stage diagnoses when surgical options may no longer be viable. The disease is driven by mutations in oncogenes, tumor suppressor genes, and DNA repair genes, with rapid growth and metastasis contributing to treatment failure. Over the past two decades, research on non-coding RNAs (ncRNAs), particularly long ncRNAs (lncRNAs), has expanded significantly, revealing their critical roles in cancer biology. LncRNAs are involved in numerous biological processes such as cell proliferation, apoptosis, metabolism, and drug resistance, and they are often abnormally expressed in various cancers, including hepatocellular carcinoma, pancreatic cancer, and bladder cancer. In CRC, lncRNAs play a regulatory role by influencing cell cycle, proliferation, apoptosis, and epithelial-mesenchymal transition, and some have been shown to affect CRC cell proliferation, invasion, and resistance to cisplatin, highlighting their potential as therapeutic targets and biomarkers in cancer treatment. This review highlights current investigations on the functions and mechanisms of lncRNAs in cisplatin resistance in CRC. Such overview is anticipated to contribute to figuring out that lncRNAs can be applied as a promising target gene to develop drug resistance and remedial efficacy.

The plasma-derived exosomal Gomafu levels are associated with psychopathological symptoms and symptomatic remission in drug-naïve patients with first-episode schizophrenia.

Long non-coding RNA (lncRNA) Gomafu has been implicated in the onset and progression of schizophrenia. In this study, we investigated the association between the plasma-derived exosomal Gomafu levels and psychopathological symptoms, as well as symptomatic remission following short-term treatment (4weeks), in patients with drug-naïve patients with first-episode schizophrenia (DFSZ). We measured the plasma-derived exosomal Gomafu levels in 65 DFSZ schizophrenia patients and 65 healthy matched controls. All DFSZ patients received aripiprazole treatment. Positive and Negative Syndrome Scale (PANSS) assessment was performed to evaluate the psychotic symptoms. Cognitive function was assessed using the validated Chinese version of the MATRICS Consensus Cognitive Battery (MCCB). We found that the expression level of plasma-derived exosomal Gomafu in DFSZ patients was significantly higher than in the healthy control group. Receiver operating characteristic (ROC) curve analysis demonstrated a high diagnostic value for plasma-derived exosomal Gomafu in identifying DFSZ, with an area under the curve (AUC) of 0.921. Multiple linear regression analysis results showed that duration of untreated psychosis (DUP), PANSS negative score, PANSS total score, MCCB-attention and vigilance score, MCCB-social cognition score, and MCCB-total score were independent influencing factors of the expression level of plasma-derived exosomal Gomafu in patients with DFSZ. After 4weeks of treatment with aripiprazole, the Gomafu levels significantly decreased in DFSZ patients. Moreover, the reduction in PANSS total score was positively correlated with the decrease in Gomafu levels. The Gomafu levels at baseline of remitters was lower than that of non-remitters. ROC curve analysis further suggested that baseline Gomafu levels could predict symptomatic remission, with an AUC of 0.695. The results of our study shows that plasma-derived exosomal Gomafu levels are ssociated with psychopathological symptoms (especially negative symptoms and cognitive impairment) and symptomatic remission with short-term aripiprazole treatment. Plasma-derived exosomal Gomafu may be a biological biomarker for DFSZ. Further studies are warranted to elucidate the mechanisms linking Gomafu to schizophrenia pathophysiology.

A Systems Bioinformatics Analysis Indicates that Disruption of the lncRNA SFTA1P Network is Consistent with Impairing Surfactant Homeostasis and Respiratory Function Observed in Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the leading global health challenges wherein novel therapeutic targets are much needed. In this systems bioinformatics study, we report that disruption of the long noncoding RNA (lncRNA) SFTA1P-centered network, respiratory gaseous exchange and surfactant-associated Biological Network (rgsBNet), is consistent with impairing surfactant homeostasis and respiratory function, and thus warrants attention for future drug discovery and development. We analyzed data from The Cancer Genome Atlas LUAD cohort to identify differentially expressed mRNAs, lncRNAs, and microRNAs (miRNAs), followed by correlational analysis to examine the coexpression network of lncRNA SFTA1P and its potential role in LUAD pathogenesis. We observed the downregulation of lncRNA SFTA1P and its coexpressed network in LUAD. Intriguingly, this network appears to be associated with disrupting surfactant homeostasis and perturbing respiratory function, suggesting a potential role in LUAD progression. Additionally, we identified key transcription factors that correlate with the expression of genes crucial for respiratory gaseous exchange and surfactant homeostasis. The attendant regulatory mechanisms suggested that SFTA1P may act as a "sponge" for certain miRNAs, sequestering them away from their mRNA targets. In conclusion, this work uncovers novel insights into the molecular mechanisms governing surfactant homeostasis in LUAD and offers a possible avenue for therapeutic interventions aimed at ameliorating lung function and improving disease management. The downregulation of lncRNA SFTA1P and its coexpressed network highlights their potential as regulators of lung function and opens doors for further investigation into their role in LUAD progression and as potential therapeutic targets.

Laryngeal Cancer in the Modern Era: Evolving Trends in Diagnosis, Treatment, and Survival Outcomes

Background/Objectives: Laryngeal cancer (LC), predominantly squamous cell carcinoma (SCC), represents a considerable health burden worldwide. Tumour subsite heterogeneity (supraglottic, glottic, subglottic) influences clinical behavior and outcomes. This review synthesizes current knowledge on epidemiology, risk factors, diagnostics, histological variants, biomarkers, treatment modalities, and survival. Results: This narrative review synthesizes current literature on the epidemiology, risk factors, diagnosis, histological variants, biomarkers, and prognosis of LC. The review highlights the critical influence of tumour sites (supraglottic, glottic, subglottic) on metastatic patterns and survival. Key risk factors of LC include tobacco and alcohol use, human papillomavirus (HPV) infection, and occupational exposures. The diagnostic process encompasses clinical examination, endoscopy, biopsy, and imaging. Several biomarkers that aid in diagnosis, treatment plan determination, and prognosis prediction have been established. These biomarkers include long noncoding RNAs, cell cycle regulators, apoptosis regulators, oncogenes, tumour suppressor genes, growth factor pathway components, angiogenic factors, structural proteins, sex hormone receptors, and immunological markers. Current treatment modalities range from organ-preserving surgery and radiotherapy to combined chemoradiotherapy and total laryngectomy. Finally, survival data are presented and stratified by stage and subsite. Conclusions: The review underscores the need for a multidisciplinary approach to LC management, integrating clinical, pathological, and molecular information to optimize patient outcomes.

The potential regulatory role of non-coding RNAs in mifepristone-induced masculinization in Takifugu rubripes gonads

BackgroundThe regulatory roles of non-coding RNAs (ncRNAs) during sex differentiation in teleosts have received widespread attention recently. Mifepristone (RU486, a progesterone antagonist), which acts as an endocrine disruptor, can affect reproduction and sex differentiation in teleosts.ResultsThe expression of ncRNAs in the gonads of tiger puffer (Takifugu rubripes) during RU486 (500 µg/g diet) induced masculinization process was examined by RNA-sequencing. A total of 4,381 long non-coding RNAs (lncRNAs), 309 circular RNAs (circRNAs), and 1,020 microRNAs (miRNAs) were identified. The expression of 41 differentially expressed (DE) lncRNAs and 20 DE miRNAs, which showed sexual dimorphic expression patterns in genetic female gonads in the control group (C-XX) vs. genetic male gonads in the control group (C-XY), were altered in genetic female gonads in the RU486 treated group (RU-XX). The genes targeted by DE ncRNAs were mainly enriched in sex-related pathways, such as calcium signaling, ovarian steroidogenesis, and cortisol synthesis and secretion. The results of co-expression and competing endogenous RNA (ceRNA) network analysis indicated that miRNAs (e.g., miR-205-z and fru-miR-122) and lncRNAs (including XR_003890915.1 and XR_003885862.1) may have pivotal roles, and lncRNAs (including XR_003890295.1, MSTRG.11750.1, and XR_003888827.1) may act as miRNA sponges, involved in the competition between miRNAs and sex-related genes during tiger puffer masculinization process. Dual luciferase reporter assay results identified that ovarian steroidogenesis related gene hsd17b1 is a downstream target of fru-miR-122. The expression of 4 lncRNAs, 4 circRNAs, and 6 miRNAs were validated by qPCR, indicating the accuracy and dependability of RNA-Seq.ConclusionsThis study provided the evidence that ncRNAs may participate in RU486-induced masculinization in T. rubripes, and may enhance our understanding of the regulatory network of sex differentiation in fugu.

NCC—An Efficient Deep Learning Architecture for Non-Coding RNA Classification

In this paper, an efficient deep-learning architecture is proposed, aiming to classify a significant category of RNA, the non-coding RNAs (ncRNAs). These RNAs participate in various biological processes and play an important role in gene regulation as well. Because of their diverse nature, the task of classifying them is a hard one in the bioinformatics domain. Existing classification methods often rely on secondary or tertiary RNA structures, which are computationally expensive to predict and prone to errors, especially for complex or novel ncRNA sequences. To address these limitations, a deep neural network classifier called NCC is proposed, which focuses solely on primary RNA sequence information. This deep neural network is appropriately trained to identify patterns in ncRNAs, leveraging well-known datasets, which are publicly available. Additionally, a ten times larger dataset than the available ones is created for better training and testing. In terms of performance, the suggested model showcases a 6% enhancement in precision compared to prior state-of-the-art systems, with an accuracy level of 92.69%, in the existing dataset. In the larger one, its accuracy rate exceeded 98%, outperforming all related tools, pointing to high prediction capability, which can act as a base for further findings in ncRNA analysis and the genomics field in general.

Bioinformatics analysis of circular RNAs associated with atrial fibrillation and their evaluation as predictive biomarkers

BackgroundCircular noncoding RNAs (circRNAs) are implicated in many human diseases, but their role in atrial fibrillation (AF) is poorly understood. In this study, we performed bioinformatics analysis of circRNA sequencing data to identify AF-related circRNAs.MethodsLeft atrial appendage (LAA) samples were obtained from patients with valvular heart disease and were categorised into the sinus rhythm (SR; n = 4) and AF (n = 4) groups. CircRNA sequencing analysis was performed to identify differentially expressed (DE) circRNAs in AF patients. Functional enrichment analysis of DE circRNAs was performed to identify enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways.ResultsWe identified 3338 DE circRNAs, including 2147 upregulated and 1191 downregulated circRNAs, in AF patients. A ceRNA network of 16 DE circRNAs, 11 DE miRNAs, and 15 DE mRNAs was constructed. Functional enrichment analyses revealed that the AF-related DE circRNAs were enriched in response to vitamin D, the potassium channel complex, delayed rectifier potassium channel activity, osteoclast differentiation, primary immunodeficiency, endocrine and other factor-regulated calcium reabsorption and other processes. ROC curve analysis identified circRNA_00324, circRNA_17225, circRNA_16305, circRNA_10233, circRNA_05499, circRNA_03183, circRNA_14211, and circRNA_18422 as potential predictive biomarkers for distinguishing AF patients from SR patients, with AUC values of 0.9138, 0.7370, 0.8526, 0.6803, 0.8163, 0.8662, 0.7664, and 0.9320, respectively.ConclusionsIn this study, we constructed an AF-related ceRNA network and identified eight circRNAs as potential predictive biomarkers of AF.

Transcriptome analysis reveals PTBP1 as a key regulator of circRNA biogenesis

BackgroundCircular RNAs (circRNAs) are a class of non-coding RNAs generated through back splicing. High expression of circRNAs is often associated with numerous abnormal cellular biological processes. However, the regulatory factors of circRNAs are not fully understood.ResultsIn this study, we identified PTBP1 as a crucial regulator of circRNA biogenesis through a comprehensive analysis of the whole transcriptome profiles across 10 diverse cell lines. Knockdown of PTBP1 led to a significant decrease in circRNA expression, concomitant with a distinct reduction in cell proliferation. To investigate the regulatory mechanism of PTBP1 on circRNA biogenesis, we constructed a minigene reporter based on SPPL3 gene. The results showed that PTBP1 can bind to the flanking introns of circSPPL3, and the mutation of PTBP1 motif impedes the back splicing of circSPPL3. Subsequently, to demonstrate that this observation is not an exception, the comprehensive regulatory effects of PTBP1 on circRNAs were confirmed by miniGFP, reflecting the necessity of the binding site in the flanking introns. Analysis of data from clinical samples showed that both PTBP1 and circRNAs exhibited substantial upregulation in acute myeloid leukemia, further demonstrating a potential role for PTBP1 in promoting circRNA biogenesis under in vivo conditions. Competitive endogenous RNA (ceRNA) network revealed that PTBP1-associated circRNAs participated in biological processes associated with cell proliferation.ConclusionsIn summary, our study is the first to identify the regulatory effect of PTBP1 on circRNA biogenesis and indicates a possible link between PTBP1 and circRNA expression in leukemia.Graphical

Novel cuproptosis-related lncRNAs risk model to predicting prognosis and guiding immunotherapy for OSCC patients

BackgroundA significant role in many cancers is played by cuproptosis, a new term for the copper-dependent regulatory cell death pattern. However, as a new research hotspot, the cuproptosis-related lncRNAs (CRLs) associated with regulation in oral squamous cell carcinoma (OSCC) patients are currently not well understood.MethodsLong noncoding RNA (lncRNA) data were downloaded from the Cancer Genome Atlas database (TCGA). The ‘LIMMA’ package in R software was used to screen for differential expression of CRLs. LASSO regression and COX regression models were used to construct prognostic signature based on 4 prognostic CRLs. Finally, the relationship of risk characteristics with immune correlation analysis, somatic mutations, PCA, biological molecular pathways and drug sensitivity was investigated.ResultsA cuproptosis-related lncRNAs prognostic signature was developed by us. Based on the risk scores, the OSCC samples were split into high- and low-risk groups using this signature. The two risk groups differed significantly in immune functions, drug sensitivity, and overall survival. The risk model showed better prognostic predictive power compared to the traditional clinicopathological signature. By qPCR trial, we also verified the expression of STARD4-AS1 in OSCC cell lines and tissues was in line with our results from this experimental screen. Through cell experiments, we have confirmed that knocking down STARD4-AS1 promotes the proliferation and migration ability of OSCC cells.ConclusionThe CRLs signature contributes to new understandings of the treatment of OSCC and is a rubost biomarker for predicting the prognosis of patients with OSCC.

MicroRNA-138-5p suppresses excitatory synaptic strength at the cerebellar input layer.

MicroRNAs are small, highly conserved non-coding RNAs that negatively regulate mRNA translation and stability. In the brain, miRNAs contribute to neuronal development, synaptogenesis, and synaptic plasticity. MicroRNA 138-5p (miR-138-5p) controls inhibitory synaptic transmission in the hippocampus and is highly expressed in cerebellar excitatory neurons. However, its specific role in cerebellar synaptic transmission remains unknown. Here, we investigated excitatory transmission in the cerebellum of mice expressing a sponge construct that sequesters endogenous miR-138-5p. Mossy fibre stimulation-evoked EPSCs in granule cells were ∼40% larger in miR-138-5p sponge mice compared to controls. Furthermore, we observed larger miniature EPSC amplitudes, suggesting an increased number of functional postsynaptic AMPA receptors. High-frequency train stimulation revealed enhanced short-term depression following miR-138-5p downregulation. Together with computational modelling, this suggests a negative regulation of presynaptic release probability. Overall, our results demonstrate that miR-138-5p suppresses synaptic strength through pre- and postsynaptic mechanisms, providing a potentially powerful mechanism for tuning excitatory synaptic input into the cerebellum. KEY POINTS: MicroRNAs are powerful regulators of mRNA translation and control key cell biological processes including synaptic transmission, but their role in regulating synaptic function in the cerebellum has remained elusive. In this study, we investigated how microRNA-138-5p (miR-138-5p) modulates excitatory transmission at adult murine cerebellar mossy fibre to granule cell synapses. Downregulation of miR-138-5p enhances excitatory synaptic strength at the cerebellar input layer and increases short-term depression. miR-138-5p exerts its regulatory function through both pre- and postsynaptic mechanisms by negatively regulating release probability at mossy fibre boutons, as well as functional AMPA receptor numbers in granule cells. These findings provide insights into the role of miR-138-5p in the cerebellum and expand our understanding of microRNA-dependent control of excitatory synaptic transmission and short-term plasticity.

Associations of circulating omentin-1 levels and long noncoding RNA MALAT1 expression with coronary heart disease in patients with type 2 diabetes mellitus

Coronary heart disease (CHD) is a severe diabetic vascular complication and the main cause of mortality among diabetes patients. Early diagnosis of CHD could prevent its development. Both omentin-1 (Oment-1) and the long noncoding RNA MALAT1 (lncRNA MALAT1) can be detected in peripheral blood and exhibit protective or detrimental effects on CHD. However, whether these two factors could be predictive of CHD in T2DM patients remains unclear. Therefore, this study aimed to investigate the associations of circulating Oment-1 levels and the expression of MALAT1 with CHD in T2DM patients and to assess their predictive efficacy. A total of 137 T2DM patients were enrolled, including 68 patients without CHD (T2DM group) and 69 patients with CHD (T2DM + CHD group). Clinical parameters were collected, and plasma Oment-1 was measured by enzyme-linked immunosorbent assay (ELISA). RNA was isolated from peripheral monocytes, and the expression of MALAT1 was determined by quantitative PCR. Cardiac function was measured by echocardiography. Compared with that in T2DM patients, the plasma Oment-1 level was significantly lower, while the expression of MALAT1 was significantly greater in T2DM + CHD patients (all P values < 0.01). Bivariate correlation analysis indicated that Oment-1 was positively correlated with the left ventricular ejection fraction (LVEF) (P < 0.01). MALAT1 expression was negatively correlated with LVEF but positively correlated with age and DM duration (P < 0.05). Binary logistic regression suggested that Oment-1 and MALAT1 were significantly associated with the presence of CHD. Receiver operating characteristic (ROC) curve analysis demonstrated that both Oment-1 (AUC = 0.663, sensitivity = 75%, specificity = 49%) and MALAT1 (AUC = 0.749, sensitivity = 73%, specificity = 66%) had significant diagnostic value for CHD among T2DM patients. Notably, the combination of Oment-1 and MALAT1 exhibited better diagnostic efficiency (AUC = 0.771, sensitivity = 66.7%, specificity = 75.3%). In conclusion, decreased circulating Oment-1 levels and increased MALAT1 expression are closely associated with CHD in T2DM patients, and their combination offers superior diagnostic efficiency, suggesting Oment-1 and MALAT1 may serve as a non-invasive tool for the early CHD detection and risk stratification in high-risk T2DM patients. Further studies are warranted to explore the pathophysiological mechanisms of Omentin-1 and MALAT1 in the pathogenesis of CHD in T2DM and to validate their clinical utility as potential biomarkers in large cohort studies.

Increased Expression of RCN1P2, TPM3P9, and HSP90AB3P as Non-Coding RNA in Gastric Cancer Linked to Proliferative, Inflammatory and Metastatic Pathways through a Competing Endogenous RNAs Network

Background: This study aimed to find pseudogenes with significant expression alterations in gastric cancer (GC) that could be implicated in the disease's development via the competing endogenous RNAs (ceRNAs) network. Methods: Pseudogenes, mRNAs, and microRNAs, whose expression changes considerably in GC specimens, were identified using the Cancer Genome Atlas (TCGA) data from 2006 to 2017 (USA). The ceRNAs network was constructed using the miRWalk, miRTarBase, and DIANA-LncBase. The cox regression test was performed to assess the correlation between candidate genes and patient prognosis. Finally, using the RT-qPCR method, the in-silico results were evaluated using GC samples and adjacent normal. Samples were collected from Imam Khomeini Hospital in Tehran (Iran) between 2020 and 2021. Results: In the cancer samples compared to the normal ones, there were 86 miRNAs, 1985 mRNAs, and 33 pseudogenes showing expression alterations, either more than or less than a twofold difference. Constructed ceRNA network demonstrated that pseudogenes such as RCN1P2, TPM3P9, and HSP90AB3P were most connected to changed mRNAs and microRNAs in GC. The analysis of the ceRNA network for each of the mentioned pseudogenes indicated that the associated mRNAs play roles in cell proliferation, inflammation, and metastatic pathways. Furthermore, elevated expression of several mRNAs linked to potential pseudogenes was linked to a poor prognosis. RT-qPCR revealed a significant increase in the expression levels of RCN1P2, TPM3P9, and HSP90AB3P in GC samples. Conclusion: The expression of RCN1P2, TPM3P9, and HSP90AB3P is dramatically enhanced in GC. They can also influence the survival rate of GC patients by regulating pathways involved in cell proliferation, inflammation, and metastasis via the ceRNAs network.

Strategies for Anticancer Treatment in p53-Mutated Head and Neck Squamous Cell Carcinoma

This Opinion summarizes the strategies for anticancer treatment in p53-mutated head and neck squamous cell carcinoma (HNSCC). It examines six strategies for anticancer treatment in p53-mutated HNSCC: 1. direct reactivation of mutated p53; 2. activation of p63; 3. activation of p73; 4. degradation of mutated p53; 5. blocking the p53-regulated oncogenic microRNA; and 6. blocking the p53-regulated oncogenic long non-coding RNA. Since HNSCC has a high p53 mutation rate compared to other types of cancers, these strategies for combating p53-mutated HNSCC may prove useful for generating new ideas or methods for developing treatments for other cancers with p53 mutations. This article also explores other factors that may impact the effectiveness of anticancer therapies in p53-mutated HNSCC.