CircGNAO1 strengthens its host gene GNAO1 expression for suppression of hepatocarcinogenesis.

Background: Hepatocellular carcinoma (HCC) is one of the most prevalent primary liver carcinoma. Guanine nucleotide-binding protein, α-activating activity polypeptide O (GNAO1) was reported to be under-expressed in HCC tissues. This study aimed to investigate the GNAO1-derived circular RNA (circRNA) and its molecular mechanisms in HCC. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot were applied to examine RNA and protein levels. Functional experiments were performed to study HCC cell proliferation, cell cycle and cellular senescence. The interactions among circGNAO1, GNAO1 and DNA methyltransferase 1 (DNMT1) were examined by mechanism assays. The methylation level was analyzed by bisulfite sequencing PCR (BSP). Results: CircGNAO1 is down-regulated and positively associated with GNAO1 in HCC tissues. Overexpression of circGNAO1 inhibits cell proliferation, induces cell cycle arrest and facilitates cell senescence in HCC cells. CircGNAO1 facilitates the progression of HCC via modulating GNAO1. Mechanistically, circGNAO1 enhances the transcription of GNAO1 by sequestering DNMT1, thereby up-regulating GNAO1 expression in HCC cells. Conclusions: CircGNAO1 up-regulates its host gene GNAO1 expression for suppression of hepatocarcinogenesis.

[Retracted] Knockdown of SNHG16 suppresses the proliferation and induces the apoptosis of leukemia cells via miR­193a­5p/CDK8.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the colony formation assay data shown in Fig. 7A on p. 1183 were strikingly similar to data appearing in different form in the following article written by different authors at different research institutes that had already been published prior to its date of submission: Lou L, Chen G, Zhong B and Liu F: Lycium barbarum polysaccharide induced apoptosis and inhibited proliferation in infantile hemangioma endothelial cells via down­regulation of PI3K/AKT signaling pathway. Biosci Rep 39: BSR20191182, 2019. In addition, possible anomalies were noted regarding the appearance of the western blots in the paper. Owing to the fact that the contentious data in the above article had already been published prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 46: 1175­1185, 2020; DOI: 10.3892/ijmm.2020.4671].

Roles of long non­coding RNA SNHG16 in human digestive system cancer (Review).

The incidence of tumors in the human digestive system is relatively high, including esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer. These malignancies arise from a complex interplay of environmental and genetic factors. Among them, long non­coding RNAs (lncRNAs), which cannot be translated into proteins, serve an important role in the development, progression, migration and prognosis of tumors. Small nucleolar RNA host gene 16 (SNHG16) is a typical lncRNA, and its relationship with digestive system tumors has been widely explored. The prevailing hypothesis suggests that the principal molecular mechanism of SNHG16 in digestive system tumors involves it functioning as a competitive endogenous RNA that interacts with other proteins, regulates various genes and influences a downstream target molecule. The present review summarizes recent research on the relationship between SNHG16 and numerous types of digestive system cancer, encompassing its biological functions, underlying mechanisms and potential clinical implications. Furthermore, it outlines the association between SNHG16 expression and pertinent risk factors, such as smoking, infection and diet. The present review indicated the promise of SNHG16 as a potential biomarker and therapeutic target in human digestive system cancer.

miR-17-92a-1 cluster host gene: a key regulator in colorectal cancer development and progression.

Colorectal cancer (CRC), recognized among the five most prevalent malignancies and most deadly cancers, manifests multifactorial influences stemming from environmental exposures, dietary patterns, age, and genetic predisposition. Although substantial progress has been made in comprehending the etiology of CRC, the precise genetic components driving its pathogenesis remain incompletely elucidated. Within the expansive repertoire of non-coding RNAs, particular focus has centered on the miR-17-92a-1 cluster host gene (MIR17HG) and its associated miRNAs, which actively participate in diverse cellular processes and frequently exhibit heightened expression in various solid tumors, notably CRC. Therefore, the primary objective of this research is to undertake an extensive inquiry into the regulatory mechanisms, structural features, functional attributes, and potential diagnostic and therapeutic implications associated with this cluster in CRC. Furthermore, the intricate interplay between this cluster and the development and progression of CRC will be explored. Our findings underscore the upregulation of the miR-17-92a-1 cluster host gene (MIR17HG) and its associated miRNAs in CRC compared to normal tissues, thus implying their profound involvement in the progression of CRC. Collectively, these molecules are implicated in critical oncogenic processes, encompassing metastatic activity, regulation of apoptotic pathways, cellular proliferation, and drug resistance. Consequently, these findings shed illuminating insights into the potential of MIR17HG and its associated miRNAs as promising targets for therapeutic interventions in the management of CRC.

Circulating Exosomes from Septic Mice Activate NF-κB/MIR17HG Pathway in Macrophages.

Circulating exosomes derived from polymicrobial sepsis contain various non-coding RNAs and proteins. Isobaric tags for a relative or absolute quantitation proteomic analysis of the exosomal content revealed 70 dysregulated proteins in the circulating exosomes from septic mice. Next-generation sequencing was used to profile the long non-coding RNA expression in primary cultured macrophages treated with exosomes obtained from the blood of septic C57BL/6 mice, and it was discovered that the nuclear factor-kappa B (NF-κB)/miR-17-92a-1 cluster host gene (MIR17HG) pathways were activated in the macrophages. The inhibition of MIR17HG expression by RNA interference resulted in significantly decreased cell viability. RNA pull-down assays of MIR17HG revealed that ten protein targets bind to MIR17HG. Interaction networks of proteins pulled down by MIR17HG were constructed using GeneMANIA, and their functions were mainly involved in ribonucleoprotein granules, type I interferons, the regulation of organelle assembly, the biosynthesis of acetyl coenzyme A, as a signal transducer and activator of transcription (STAT) protein phosphorylation, and mRNA splicing. Furthermore, RNA interference inhibited MIR17HG expression, resulting in significantly decreased cell survival. In conclusion, this work discovered considerable MIR17HG overexpression in macrophages treated with circulating exosomes from sepsis-affected animals. This study's findings assist us in comprehending the role of exosomes in modulating inflammatory responses and mediating pathogenic pathways in macrophages during sepsis.

Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia.

AIMS: Long non-coding RNA (LncRNA) small nucleolar RNA host gene 18 (SNHG18) has been widely implicated in cancers. However, little is known about its functional involvement in vascular diseases. Herein, we attempted to explore a role for SNHG18 in modulating vascular smooth muscle cell (VSMC) contractile phenotype and injury-induced neointima formation. METHODS AND RESULTS: Analysis of single-cell RNA sequencing and transcriptomic datasets showed decreased levels of SNHG18 in injured and atherosclerotic murine and human arteries, which is positively associated with VSMC contractile genes. SNHG18 was upregulated in VSMCs by TGFß1 through transcription factors Sp1 and SMAD3. SNHG18 gene gain/loss-of-function studies revealed that VSMC contractile phenotype was positively regulated by SNHG18. Mechanistic studies showed that SNHG18 promotes a contractile VSMC phenotype by up-regulating miR-22-3p. SNHG18 up-regulates miR-22 biogenesis and miR-22-3p production by competitive binding with the A-to-I RNA editing enzyme, adenosine deaminase acting on RNA-2 (ADAR2). Surprisingly, we observed that ADAR2 inhibited miR-22 biogenesis not through increasing A-to-I editing within primary miR-22, but by interfering with the binding of microprocessor complex subunit DGCR8 to primary miR-22. Importantly, perivascular SNHG18 overexpression in the injured vessels dramatically up-regulated the expression levels of miR-22-3p and VSMC contractile genes, and prevented injury-induced neointimal hyperplasia. Such modulatory effects were reverted by miR-22-3p inhibition in the injured arteries. Finally, we observed a similar regulator role for SNHG18 in human VSMCs and a decreased expression level of both SNHG18 and miR-22-3p in diseased human arteries; and we found that the expression level of SNHG18 was positively associated with that of miR-22-3p in both healthy and diseased human arteries. CONCLUSION: We demonstrate that SNHG18 is a novel regulator in governing VSMC contractile phenotype and preventing injury-induced neointimal hyperplasia. Our findings have important implications for therapeutic targeting snhg18/miR-22-3p signalling in vascular diseases.

Long noncoding RNA small nucleolar RNA host gene 5 facilitates neuropathic pain in spinal nerve injury by promoting SCN9A expression via CDK9.

This study aims to explore the functions and mechanisms of long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) in chronic constriction injury (CCI)-induced neuropathic pain (NP). An NP rat model was established using the CCI method and the NP severity was evaluated by paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). The expression of SNHG5, CDK9, and SCN9A was quantified in rat dorsal root ganglion, in addition to the detections of apoptosis, pathological changes, neuron number, and the co-localization of Nav1.7 and cleaved caspase-3 with NeuN. In ND7/23 cells, the apoptosis and lactate dehydrogenase concentration were assessed, as well as the relationship between SNHG5, CDK9, and SCN9A. In the dorsal root ganglion of CCI-treated rats, SNHG5 and SCN9A were upregulated and downregulation of SNHG5 suppressed SCN9A expression, increased the PWT and PWL, blocked neuroinflammation and neuronal apoptosis, and alleviated NP. Mechanistically, SNHG5 recruited CDK9 to enhance SCN9A-encoded Nav1.7 expression and promoted peripheral neuronal apoptosis and injury. In addition, SCN9A overexpression nullified the alleviative effects of SNHG5 deficiency on NP and neuron loss in CCI rats. In conclusion, SNHG5 promotes SCN9A-encoded Nav1.7 expression by recruiting CDK9, thereby facilitating neuron loss and NP after spinal nerve injury, which may offer a promising target for the management of NP.

Coptisine prevents angiotensin II­induced endothelial cell injury and senescence via the lncRNA SNHG12/miR­603/NAMPT pathway.

Atherosclerosis (AS) is a major health problem and targeting the associated molecular pathways is critical for developing therapies. The present study investigated the effect of coptisine on human umbilical vein endothelial cells (HUVECs) in response to angiotensin II (Ang II) induction by focusing on cellular senescence, apoptosis and inflammation. HUVECs were treated with different Ang II concentrations and long non-coding RNA small nucleolar RNA host gene 12 (SNHG12), microRNA (miRNA/miR)-603 and nicotinamide phosphoribosyltransferase (NAMPT) expressions were assessed. Cell viability, nicotinamide adenine dinucleotide (NAD+) levels, senescence, apoptosis and inflammation were assessed. The interactions among SNHG12, miR-603 and NAMPT were investigated using dual-luciferase reporter gene assays and RNA pull-down experiments. Coptisine treatment increased SNHG12 expression and attenuated Ang II-induced adverse effects in HUVECs. SNHG12 silencing abrogated coptisine's protective effects, indicating that SNHG12 is a key mediator. SNHG12 targets miR-603, which then directly targets NAMPT, an age-related gene involved in NAD(+) regulation. Coptisine modulated the SNHG12/miR-603/NAMPT pathway and miR-603 inhibition enhanced the protective effects of coptisine. NAMPT overexpression reversed the negative effects of miR-603 and enhanced the protective effect of the miR-603 inhibitor. Finally, the protective mechanism of coptisine is linked to the regulation of NAD(+), sirtuin 3 (SIRT3) and p53. Coptisine treatment counteracted the AngII-induced increase in SIRT3 and p53 protein levels, whereas the miR-603 inhibitor potentiated the effect of coptisine. SNHG12 knockdown partially abolished these effects, which were reversed by NAMPT overexpression. In conclusion, the present study revealed a novel protective mechanism involving the SNHG12/miR-603/NAMPT pathway in HUVECs exposed to Ang II, highlighting the potential therapeutic application of coptisine in treating atherosclerosis. These results suggested that coptisine exerts its protective effects by modulating the SNHG12/miR-603/NAMPT axis, which ultimately affects the regulation of NAD(+), SIRT3 and p53. Future studies should explore the potential of the SNHG12/miR-603/NAMPT pathway as a target for developing novel AS therapies.

CircBRD7 attenuates tumor growth and metastasis in nasopharyngeal carcinoma via epigenetic activation of its host gene.

BRD7 was identified as a tumor suppressor in nasopharyngeal carcinoma (NPC). Circular RNAs (CircRNAs) are involved in the occurrence and development of NPC as oncogenes or tumor suppressors. However, the function and mechanism of the circular RNA forms derived from BRD7 in NPC are not well understood. In this study, we first identified that circBRD7 was a novel circRNA derived from BRD7 that inhibited cell proliferation, migration, invasion of NPC cells, as well as the xenograft tumor growth and metastasis in vivo. Mechanistically, circBRD7 promoted the transcriptional activation and expression of BRD7 by enhancing the enrichment of histone 3 lysine 27 acetylation (H3K27ac) in the promoter region of its host gene BRD7, and BRD7 promoted the formation of circBRD7. Therefore, circBRD7 formed a positive feedback loop with BRD7 to inhibit NPC development and progression. Moreover, restoration of BRD7 expression rescued the inhibitory effect of circBRD7 on the malignant progression of NPC. In addition, circBRD7 demonstrated low expression in NPC tissues, which was positively correlated with BRD7 expression and negatively correlated with the clinical stage of NPC patients. Taken together, circBRD7 attenuates the tumor growth and metastasis of NPC by forming a positive feedback loop with its host gene BRD7, and targeting the circBRD7/BRD7 axis is a promising strategy for the clinical diagnosis and treatment of NPC.

Andrographolide anti-proliferation and metastasis of hepatocellular carcinoma through LncRNA MIR22HG regulation.

Hepatocellular carcinoma (HCC) treatment is a major challenge. Although andrographolide (Andro) has an anti-proliferation effect on HCC, its underlying mechanism is not yet elucidated, and whether Andro can inhibit HCC metastasis has not been reported. The present study aimed to clarify whether Andro inhibits SK-Hep-1 cell proliferation and HCC metastasis, and the mechanisms. The results showed that Andro significantly reduced the survival of HCC cells and tumor weight and volume in tumor-bearing nude mice. Andro also triggered apoptosis of HCC cells and upregulated MIR22HG, Cleaved Caspase 9/7/3 expression levels, and downregulated BCL-2 mRNA, BCL-2 expression levels. Knockdown of MIR22HG or overexpression of HuR attenuated the effects of Andro on the signal transduction of mitochondrial apoptotic pathway and proliferation ability in HCC cells. Moreover, Andro significantly reduced the invasive ability of the cells and the level of HCC cell lung metastasis, upregulated miR-22-3p expression level and downregulated HMGB1 and MMP-9 expression levels. MIR22HG or miR-22-3p knockdown attenuated the effects of Andro on the signaling of HMGB1/MMP-9 pathway and invasive ability in HCC cells, while the overexpression of HMGB1 attenuated the inhibitory effects of Andro on the MMP-9 expression level and invasive ability in HCC cells. Thus, the regulation of MIR22HG-HuR/BCL-2 and MIR22HG/HMGB1 signaling pathways is involved in the anti-HCC proliferation and metastasis effects of Andro. This study provided a new pharmacological basis for Andro in HCC treatment and, for the first time, identified a natural product molecule capable of positively regulating MIR22HG, which has a robust biological function.

Candidate circRNAs related to skeletal muscle development in Dazu black goats.

Circular RNA (CircRNA), as a classical noncoding RNA, has been proven to regulate skeletal muscle development (SMD). However, the molecular genetic basis of circRNA regulation in muscle cells remains unclear. In this study, the expression patterns of circRNAs in the longissimus dorsi muscle at embryonic day 75 and postnatal day 1 in DBGs were investigated to identify the key circRNAs that play an important role in SMD in goats. A total of 140 significantly and differentially expressed circRNAs (DEcircRNAs) were identified among the groups at different developmental stages. Among the 116 host genes (HGs) of DEcircRNAs, 76 were significantly and differentially expressed, which was confirmed by previous RNA_seq data. Furthermore, the expression pattern of 10 DEcircRNAs with RT-qPCR was verified, which showed 80% concordance rate with that of RNA_seq datasets. Moreover, the authenticity of seven randomly selected DEcircRNAs was verified by PCR Sanger sequencing. Based on the functional annotation results, among the 76 significantly and differentially expressed HGs, 74 were enriched in 845 GO terms, whereas 35 were annotated to 85 KEGG pathways. The results of this study could provide a comprehensive understanding of the genetic basis of circRNAs involved in SMD and muscle growth.

Cytolethal distending toxin B inoculation leads to distinct gut microtypes and IBS-D-like microRNA-mediated gene expression changes in a rodent model.

Diarrhea-predominant irritable bowel syndrome (IBS-D), associated with increased intestinal permeability, inflammation, and small intestinal bacterial overgrowth, can be triggered by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by gastroenteritis-causing pathogens and may underlie IBS-D development, through molecular mimicry with vinculin. Here, we examine the effects of exposure to CdtB alone on gut microbiome composition, host intestinal gene expression, and IBS-D-like phenotypes in a rat model. CdtB-inoculated rats exhibited increased anti-CdtB levels, which correlated with increased stool wet weights, pro-inflammatory cytokines (TNFα, IL2) and predicted microbial metabolic pathways including inflammatory responses, TNF responses, and diarrhea. Three distinct ileal microbiome profiles (microtypes) were identified in CdtB-inoculated rats. The first microtype (most like controls) had altered relative abundance (RA) of genera Bifidobacterium, Lactococcus, and Rothia. The second had lower microbial diversity, higher Escherichia-Shigella RA, higher absolute E. coli abundance, and altered host ileal tissue expression of immune-response and TNF-response genes compared to controls. The third microtype had higher microbial diversity, higher RA of hydrogen sulfide (H2S)-producer Desulfovibrio, and increased expression of H2S-associated pain/serotonin response genes. All CdtB-inoculated rats exhibited decreased ileal expression of cell junction component mRNAs, including vinculin-associated proteins. Significantly, cluster-specific microRNA-mRNA interactions controlling intestinal permeability, visceral hypersensitivity/pain, and gastrointestinal motility genes, including several previously associated with IBS were seen. These findings demonstrate that exposure to CdtB toxin alone results in IBS-like phenotypes including inflammation and diarrhea-like stool, decreased expression of intestinal barrier components, and altered ileal microtypes that influenced changes in microRNA-modulated gene expression and predicted metabolic pathways consistent with specific IBS-D symptoms.

[Research Progress of LncRNA SNHGs in Regulating the Biological Behavior 
of Non-small Cell Lung Cancer].

Lung cancer is one of the malignant tumors with the highest incidence and mortality rate in China, and its occurrence and development mechanism and treatment methods are the current research focuses. In recent years, the emergence of drugs targeting various tumor driver genes has significantly improved patients' survival and quality of life, setting off a wave of research on new therapeutic targets. Among them, long non-coding RNA (lncRNA) plays a crucial role in the malignant behavior of tumors, which has attracted widespread attention. Shown by a large number of studies, partial members of lncRNA small nucleolar RNA host gene (SNHG) family are aberrantly expressed in many maliglant tumors including non-small cell lung cancer (NSCLC) and participate in cell proliferation, invasion and migration, which may act as a new diagnostic and prognostic biomarker and can be a therapeutic target of NSCLC. In this review, we comprehensively summarize and explore the recent investigation of SNHGs in NSCLC in order to provide new ideas for the diagnosis and treatment of NSCLC.
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Application of Host-Depleted Nanopore Metagenomic Sequencing in the Clinical Detection of Pathogens in Pigs and Cats.

Metagenomic sequencing is a valuable tool for non-specifically detecting various microorganisms in samples, offering unique advantages for detecting emerging pathogens, fastidious or uncultivable pathogens, and mixed infections. It has recently been applied to clinically detect pathogenic microorganisms in animals; however, the high proportion of host genes, expensive sequencing equipment, and the complexity of sequencing and data analysis methods have limited its clinical utility. In this study, a combination of tissue homogenization and nuclease digestion was employed to remove host genes from pig and cat samples; DNA and RNA were then extracted and subjected to nonselective PCR amplification to simultaneously detect DNA and RNA pathogen genomes using R9.4.1 or R10.4.1 flow cells on the MinION platform. Real-time pathogen detection was conducted using EPI2M WIMP, and viral genome assembly was performed using NanoFilt, minimap2, samtools, and ivar. Pathogens in five clinical samples (serum, nasopharyngeal swab, feces, or ascites) from cats and four clinical samples (lung or small intestine tissue) from pigs were examined by metagenomic sequencing, and the results were consistent with those obtained by PCR and bacterial culture. Additionally, we detected four viruses and three bacteria that may be associated with diseases. A comparison of results before and after host gene removal in three samples showed a 9-50% reduction in host genes. We also compared the assembly efficiency of six virus genomes and found that data volumes ranging from 3.3 to 98.3 MB were sufficient to assemble >90% of the viral genomes. In summary, this study utilized optimized nanopore metagenomic sequencing and analysis methods to reduce host genes, decrease the required data volume for sequencing analysis, and enable real-time detection to determine when to stop sequencing. The streamlined sequencing and analysis process overcomes barriers to the veterinary clinical application of metagenomic sequencing and provides a reference for clinical implementation.

Integrated analysis reveals a potential cuproptosis-related ceRNA axis SNHG17/miR-29a-3p/GCSH in prostate adenocarcinoma.

Cuproptosis is a novel form of programmed cell death. The role and mechanism of cuproptosis-related genes in prostate adenocarcinoma have not been fully understood. In this study, a series of bioinformatic analyses were performed. Consequently, glycine cleavage system protein H with high expression and unfavorable prognosis was regarded as the most potential cuproptosis-related gene in prostate adenocarcinoma. Moreover, glycine cleavage system protein H might be a promising indicator for predicting leuprolide sensitivity in prostate adenocarcinoma and three potential drugs targeting glycine cleavage system protein H were identified. Enrichment analysis revealed that glycine cleavage system protein H-correlated genes were significantly enriched in tricarboxylic acid cycle-related pathways. Subsequently, small nucleolar RNA host gene 17/miR-29a-3p axis was found to partially account for overexpression of glycine cleavage system protein H in prostate adenocarcinoma. Collectively, the current study elucidated a potential cuproptosis-related competing endogenous RNA axis small nucleolar RNA host gene 17/miR-29a-3p/glycine cleavage system protein H in prostate adenocarcinoma.

Human mRNA in saliva can correctly identify individuals harboring acute infection.

The COVID-19 pandemic demonstrated the poor ability of body temperature to reliably identify SARS-CoV-2-infected individuals, an observation that has been made before in the context of other infectious diseases. While acute infection does not always cause fever, it does reliably drive host transcriptional responses as the body responds at the site of infection. These transcriptional changes can occur both in cells that are directly harboring replicating pathogens and in cells elsewhere that receive a molecular signal that infection is occurring. Here, we identify a core set of approximately 70 human genes that are together upregulated in cultured human cells infected by a broad array of viral, bacterial, and fungal pathogens. We have named these "core response" genes. In theory, transcripts from these genes could serve as biomarkers of infection in the human body, in a way that is agnostic to the specific pathogen causing infection. As such, we perform human studies to show that these infection-induced human transcripts can be measured in the saliva of people harboring different types of infections. The number of these transcripts in saliva can correctly classify infection status (whether a person harbors an infection) 91% of the time. Furthermore, in the case of SARS-CoV-2 specifically, the number of core response transcripts in saliva correctly identifies infectious individuals even when enrollees, themselves, are asymptomatic and do not know they are infected.IMPORTANCEThere are a variety of clinical and laboratory criteria available to clinicians in controlled healthcare settings to help them identify whether an infectious disease is present. However, in situations such as a new epidemic caused by an unknown infectious agent, in health screening contexts performed within communities and outside of healthcare facilities or in battlefield or potential biowarfare situations, this gets more difficult. Pathogen-agnostic methods for rapid screening and triage of large numbers of people for infection status are needed, in particular methods that might work on an easily accessible biospecimen like saliva. Here, we identify a small, core set of approximately 70 human genes whose transcripts serve as saliva-based biomarkers of infection in the human body, in a way that is agnostic to the specific pathogen causing infection.

The Functions and Mechanisms of Long Non-coding RNA SNHGs in Gastric Cancer.

Gastric cancer is one of the most common malignancies worldwide. Despite significant advancements in surgical and adjuvant treatments, patient prognosis remains unsatisfactory. Long non-coding RNAs (lncRNAs) are a class of RNA molecules that lack protein-coding capacity but can participate in various mechanisms of tumor malignancy. Among them, small nucleolar host genes (SNHGs) represent a subgroup of lncRNAs. Studies have revealed their involvement not only in gastric cancer cell proliferation, invasion, migration, epithelialmesenchymal transition (EMT), and apoptosis but also in chemotherapy resistance and tumor stemness. This review comprehensively summarizes the biological functions, molecular mechanisms, and clinical significance of SNHGs in gastric cancer. It provides novel insights into potential biomarkers and therapeutic targets for the exploration of gastric cancer.

Long Non-coding RNA SNHG7 Suppresses Inflammation and Apoptosis of Chondrocytes Through Inactivating of p38 MAPK Signaling Pathway in Osteoarthritis.

This study aims to explore the molecular mechanism of LncRNA SNHG7 in Osteoarthritis (OA). Cartilage tissues of OA patients or patients with trauma or amputation were collected. Compared to normal cartilage tissues, SNHG7 was downregulated while miR-324-3p was upregulated in cartilage tissues of OA patients. IL-1ß was used to induce damage to chondrocytes and treatment with IL-1ß reduced SNHG7 expression in OA chondrocytes. In IL-1ß-treated OA chondrocytes, SNHG7 overexpression reduced the levels of TNF-α and IL-6, inhibited cell apoptosis, and increased cell viability. Additionally, the luciferase reporter assay proved that SNHG7 upregulated dual-specificity phosphatase 1 (DUSP1) by sponging miR-324-3p, thereby inactivating the p38 MAPK signaling pathway by regulating the miR-324-3p/DUSP1 axis. Anisomycin (a p38 MAPK activator) enhanced OA chondrocytes inflammation, promoted cell apoptosis, and reduced cell viability; however, this was reversed by SNHG7 overexpression. This study demonstrates that the SNHG7/miR-324-3p/DUSP1 axis suppresses OA chondrocytes inflammation and apoptosis by inhibiting the p38 MAPK signaling pathway. Thus, this study indicates that SNHG7 is a novel target for OA treatment.

Intronic small nucleolar RNAs regulate host gene splicing through base pairing with their adjacent intronic sequences.

BACKGROUND: Small nucleolar RNAs (snoRNAs) are abundant noncoding RNAs best known for their involvement in ribosomal RNA maturation. In mammals, most expressed snoRNAs are embedded in introns of longer genes and produced through transcription and splicing of their host. Intronic snoRNAs were long viewed as inert passengers with little effect on host expression. However, a recent study reported a snoRNA influencing the splicing and ultimate output of its host gene. Overall, the general contribution of intronic snoRNAs to host expression remains unclear. RESULTS: Computational analysis of large-scale human RNA-RNA interaction datasets indicates that 30% of detected snoRNAs interact with their host transcripts. Many snoRNA-host duplexes are located near alternatively spliced exons and display high sequence conservation suggesting a possible role in splicing regulation. The study of the model SNORD2-EIF4A2 duplex indicates that the snoRNA interaction with the host intronic sequence conceals the branch point leading to decreased inclusion of the adjacent alternative exon. Extended SNORD2 sequence containing the interacting intronic region accumulates in sequencing datasets in a cell-type-specific manner. Antisense oligonucleotides and mutations that disrupt the formation of the snoRNA-intron structure promote the splicing of the alternative exon, shifting the EIF4A2 transcript ratio away from nonsense-mediated decay. CONCLUSIONS: Many snoRNAs form RNA duplexes near alternative exons of their host transcripts, placing them in optimal positions to control host output as shown for the SNORD2-EIF4A2 model system. Overall, our study supports a more widespread role for intronic snoRNAs in the regulation of their host transcript maturation.

Hepatitis B vaccine delivered by microneedle patch: Immunogenicity in mice and rhesus macaques.

Vaccination against hepatitis B using a dissolving microneedle patch (dMNP) could increase access to the birth dose by reducing expertise needed for vaccine administration, refrigerated storage, and safe disposal of biohazardous sharps waste. In this study, we developed a dMNP to administer hepatitis B surface antigen (HBsAg) adjuvant-free monovalent vaccine (AFV) at doses of 5 µg, 10 µg, and 20 µg, and compared its immunogenicity to vaccination with 10 µg of standard monovalent HBsAg delivered by intramuscular (IM) injection either in an AFV format or as aluminum-adjuvanted vaccine (AAV). Vaccination was performed on a three dose schedule of 0, 3, and 9 weeks in mice and 0, 4, and 24 weeks in rhesus macaques. Vaccination by dMNP induced protective levels of anti-HBs antibody responses (≥10 mIU/ml) in mice and rhesus macaques at all three HBsAg doses studied. HBsAg delivered by dMNP induced higher anti-HBsAg antibody (anti-HBs) responses than the 10 µg IM AFV, but lower responses than 10 µg IM AAV, in mice and rhesus macaques. HBsAg-specific CD4+ and CD8+ T cell responses were detected in all vaccine groups. Furthermore, we analyzed differential gene expression profiles related to each vaccine delivery group and found that tissue stress, T cell receptor signaling, and NFκB signaling pathways were activated in all groups. These results suggest that HBsAg delivered by dMNP, IM AFV, and IM AAV have similar signaling pathways to induce innate and adaptive immune responses. We further demonstrated that dMNP was stable at room temperature (20 °C-25 °C) for 6 months, maintaining 67 ± 6 % HBsAg potency. This study provides evidence that delivery of 10 µg (birth dose) AFV by dMNP induced protective levels of antibody responses in mice and rhesus macaques. The dMNPs developed in this study could be used to improve hepatitis B birth dose vaccination coverage levels in resource limited regions to achieve and maintain hepatitis B elimination.