Circular RNAs in laryngeal cancer.

Laryngeal cancer remains a significant global health concern, with poor prognosis for advanced-stage disease highlighting the need for novel diagnostic, prognostic, and therapeutic approaches. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs, have emerged as important regulators of gene expression and cellular processes in various cancers, including laryngeal cancer. This review summarizes the current understanding of circRNAs in laryngeal cancer, covering their biogenesis, regulatory mechanisms, and potential clinical applications. We explore the diverse functions of circRNAs, including their roles as miRNA sponges, protein interactors, and direct mRNA regulators, and their influence on key cellular processes such as proliferation, invasion, and metastasis. The review highlights promising circRNAs as diagnostic and prognostic biomarkers, as well as potential therapeutic targets. We also outline current strategies for circRNA modulation, including suppression techniques like RNA interference and CRISPR/Cas systems, and overexpression methods using vectors and synthetic circRNAs.

Emerging roles of CircRNA-miRNA networks in cancer development and therapeutic response.

The complex interplay of epigenetic factors is essential in regulating the hallmarks of cancer and orchestrating intricate molecular interactions during tumor progression. Circular RNAs (circRNAs), known for their covalently closed loop structures, are non-coding RNA molecules exceptionally resistant to enzymatic degradation, which enhances their stability and regulatory functions in cancer. Similarly, microRNAs (miRNAs) are endogenous non-coding RNAs with linear structures that regulate cellular biological processes akin to circRNAs. Both miRNAs and circRNAs exhibit aberrant expressions in various cancers. Notably, circRNAs can function as sponges for miRNAs, influencing their activity. The circRNA/miRNA interaction plays a pivotal role in the regulation of cancer progression, including in brain, gastrointestinal, gynecological, and urological cancers, influencing key processes such as proliferation, apoptosis, invasion, autophagy, epithelial-mesenchymal transition (EMT), and more. Additionally, this interaction impacts the response of tumor cells to radiotherapy and chemotherapy and contributes to immune evasion, a significant challenge in cancer therapy. Both circRNAs and miRNAs hold potential as biomarkers for cancer prognosis and diagnosis. In this review, we delve into the circRNA-miRNA circuit within human cancers, emphasizing their role in regulating cancer hallmarks and treatment responses. This discussion aims to provide insights for future research to better understand their functions and potentially guide targeted treatments for cancer patients using circRNA/miRNA-based strategies.

Targeting LINC00665/miR-199b-5p/SERPINE1 axis to inhibit trastuzumab resistance and tumorigenesis of gastric cancer via PI3K/AKt pathway.

Long noncoding RNAs (lncRNAs) serve as critical mediators of tumor progression and drug resistance in cancer. Herein, we identified a lncRNA, LINC00665, associated with trastuzumab resistance and development in gastric cancer (GC). LINC00665 was highly expressed in GC tissues and high expression of LINC00665 was correlated with poor prognosis. LINC00665 knockdown was verified to suppress migration, invasion, and resistance to trastuzumab in GC. Furthermore, we found that LINC00665 participates in the infiltration of naive B cells, mast cells, and T follicular helper (Tfh) cells. Mechanistically, LINC00665 was confirmed to regulate tumorigenesis and trastuzumab resistance by activating PI3K/AKt pathway. LINC00665 sponged miR-199b-5p to interact with SERPINE1 expression, resulting in the increase of phosphorylation of AKt, thus participating in the PI3K/AKt pathway. To summarize, LINC00665 facilitated the tumorigenesis and trastuzumab resistance of GC by sponging miR-199b-5p and promoting SERPINE1 expression, which further activated PI3K/AKt signaling; this finding reveals a new mechanism by which LINC00665 modulates tumor development and drug resistance in GC.

Roles of small peptides encoded by non-coding RNAs in tumor invasion and migration.

Non-coding RNAs (ncRNAs), which are usually considered not to encode proteins, are widely involved in important activities including signal transduction and cell proliferation. However, recent studies have shown that small peptides encoded by ncRNAs (SPENs) have important roles in the development of malignant tumors. Some SPENs participate in the regulation of skeleton reorganization, intercellular adhesion, signaling and other processes of tumor cells, with effects on the invasive and migratory abilities of the cells. Therefore, SPENs have potential applications as therapeutic targets and biomarkers of malignant tumors. Invasion and migration of malignant tumor cells are the main reasons for poor prognosis of cancer patients and represent the most challenging aspects of treatment of malignant tumors. Currently, the main treatments for tumors include surgery, radiotherapy, targeted drug therapy. Surgery, however, is reserved for early stages of cancer and carries risks and costs. Radiotherapy and targeted therapy have serious side effects. This review describes the mechanisms of SPENs and their roles in tumor invasion and migration, with the aim of providing new targets for tumor diagnosis and treatment.

Representation of non-coding RNA-mediated regulation of gene expression using the Gene Ontology.

Regulatory non-coding RNAs (ncRNAs) are increasingly recognized as integral to the control of biological processes. This is often through the targeted regulation of mRNA expression, but this is by no means the only mechanism through which regulatory ncRNAs act. The Gene Ontology (GO) has long been used for the systematic annotation of protein-coding and ncRNA gene function, but rapid progress in the understanding of ncRNAs meant that the ontology needed to be revised to accurately reflect current knowledge. Here, a targeted effort to revise GO terms used for the annotation of regulatory ncRNAs is described, focusing on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs). This paper provides guidance to biocurators annotating ncRNA-mediated processes using the GO and serves as background for researchers wishing to make use of the GO in their studies of ncRNAs and the biological processes they regulate.

Quantitative detection of circular RNA and microRNA at point-of-care using droplet digital CRISPR/Cas13a platform.

Circular RNA (circRNA) and microRNA (miRNA) are both non-coding RNAs (ncRNAs) that serve as biomarkers for cancer diagnosis and prognosis. Quantitative detection of these ncRNAs is of particular importance to elucidate the functional mechanisms and evaluate their potential as biomarkers. However, the inherent structures of circRNA and miRNA are different from the mRNA, conventional qRT-PCR is unsuitable for the detection of these ncRNAs. Here, we propose a sensitive method for quantitative detection of circRNA and miRNA using polydisperse droplet digital CRISPR/Cas13a (PddCas13a). It can achieve limits of detection (LOD) as low as ∼10 aM without polymerase-based amplification. To efficiently detect the circRNA and miRNA in real samples, we use a chemically modified crRNA to enhance the stability of crRNA and improve the performance of Cas13a in complex environments containing contaminants. By integrating an extraction-free procedure with PddCas13a, we experimentally demonstrate the applicability of PddCas13a by testing clinical samples. Furthermore, we develop an automated and portable instrument for PddCas13a and verify its applicability for the detection of circRNA and miRNA from exosomes in point-of-care (POC) setting. This is the first report to detect the circRNA and miRNA simultaneously in POC setting. We envision this platform could promote the research of ncRNAs.

The LINC00319 binding to STAT3 promotes the cell proliferation, migration, invasion and EMT process in oral squamous cell carcinoma.

BACKGROUND: Long non-coding RNA LINC00319 has been implicated in the progression of various cancers, including oral squamous cell carcinoma (OSCC). While our previous work has revealed some aspects of LINC00319's role in OSCC, including its upregulation and involvement in a competing endogenous RNA (ceRNA) mechanism, the full extent of its functions and regulatory mechanisms in OSCC progression remain to be fully elucidated. OBJECTIVE: This study aimed to investigate the function of LINC00319 in OSCC and its potential interaction with the STAT3 signaling pathway, thus uncovering novel regulatory mechanisms and therapeutic targets. METHODS: Bioinformatics analysis was performed using TCGA data to evaluate LINC00319 expression in OSCC tissues and its correlation with STAT3 signaling. The direct binding between LINC00319 and STAT3 was examined by RNA pull-down, FISH, and RIP assays. Functional experiments, including CCK-8, transwell migration and invasion assays, and western blot analysis of EMT markers and STAT3 pathway activation, were conducted to assess the effects of LINC00319 on OSCC cell behaviors and its interaction with the STAT3 signaling pathway. In vivo xenograft models were established to validate the role of LINC00319 in tumor growth and STAT3 activation. RESULTS: LINC00319 expression was significantly upregulated in OSCC tissues compared to normal tissues, and high LINC00319 expression correlated with STAT3 signaling activation. Mechanistically, LINC00319 directly bound to STAT3 protein and promoted its phosphorylation at Tyr705. LINC00319 overexpression enhanced, while its knockdown suppressed, the proliferation, migration, invasion, and EMT of OSCC cells. These oncogenic effects were mediated through STAT3 activation and could be reversed by the STAT3 inhibitor stattic. In vivo experiments further confirmed that LINC00319 silencing inhibited tumor growth and STAT3 phosphorylation. CONCLUSION: This study uncovers that LINC00319 promotes OSCC tumorigenesis by directly binding to and activating STAT3 signaling. These findings provide new insights into the regulatory mechanisms of STAT3 by long non-coding RNAs and highlight the potential of LINC00319 as a biomarker and therapeutic target in OSCC.

Stress-Induced Evolution of the Nucleolus: The Role of Ribosomal Intergenic Spacer (rIGS) Transcripts.

It became clear more than 20 years ago that the nucleolus not only performs the most important biological function of assembling ribonucleic particles but is also a key controller of many cellular processes, participating in cellular adaptation to stress. The nucleolus's multifunctionality is due to the peculiarities of its biogenesis. The nucleolus is a multilayered biomolecular condensate formed by liquid-liquid phase separation (LLPS). In this review, we focus on changes occurring in the nucleolus during cellular stress, molecular features of the nucleolar response to abnormal and stressful conditions, and the role of long non-coding RNAs transcribed from the intergenic spacer region of ribosomal DNA (IGS rDNA).

The Role of MicroRNA in the Pathophysiology and Diagnosis of Viral Myocarditis.

Myocarditis is a non-ischemic condition with a heterogeneous etiology, clinical course and prognosis. The most common etiology of myocarditis are viral infections, whereas the most severe complications are acute and chronic heart failure and sudden cardiac death. The heterogeneous clinical course of the disease, as well as the availability and costs of diagnostic tools such as cardiac magnetic resonance and endomyocardial biopsy, hinder the diagnosis of myocarditis and its underlying cause. Non-coding RNAs such as micro-RNAs (miRNAs; miR) have been shown to be involved in the disease's pathophysiology; however, their potential in disease diagnosis and treatment should also be considered. Non-coding RNAs are RNAs that are not translated into proteins, and they have the ability to regulate several intracellular pathways. MiRNAs regulate gene expression by binding with their targets and inhibiting protein synthesis by interfering with the translation of coding genes or causing the degradation of messenger RNA. Several miRNAs, such as miR-1, -133, -21, -15, -98, -126, -155, -148, -203, -208, -221, -222, -203 and -590, have been shown to be involved in the pathophysiology of viral myocarditis (VMC), and some of them have been shown to have diagnostic abilities. This article summarizes the available data on miRNAs and their associations with VMC.

Rfam 15: RNA families database in 2025.

The Rfam database, a widely-used repository of non-coding RNA (ncRNA) families, has undergone significant updates in release 15.0. This paper introduces major improvements, including the expansion of Rfamseq to 26,106 genomes, a 76% increase, incorporating the latest UniProt reference proteomes and additional viral genomes. Sixty-five RNA families were enhanced using experimentally determined 3D structures, improving the accuracy of consensus secondary structures and annotations. R-scape covariation analysis was used to refine structural predictions in 26 families. Gene Ontology and Sequence Ontology annotations were comprehensively updated, increasing GO term coverage to 75% of families. The release adds 14 new Hepatitis C Virus RNA families and completes microRNA family synchronisation with miRBase, resulting in 1,603 microRNA families. New data types, including FULL alignments, have been implemented. Integration with APICURON for improved curator attribution and multiple website enhancements further improve user experience. These updates significantly expand Rfam's coverage and improve annotation quality, reinforcing its critical role in RNA research, genome annotation, and the development of machine learning models. Rfam is freely available at https://rfam.org.

Long non-coding RNA UCA1 Knockdown Assisted by CRISPR/Cas9 in Female Cancer Cell Lines Increases Mir-143 Tumor-Suppressor.

Background: The lncRNAs has been linked to several malignancies, including breast cancer. Our objective was to investigate the impact of urothelial carcinoma associated 1 (UCA1) on cellular growth and death by a CRISPR/Cas9 knockdown technique. Methods: In 2020, the CHOPCHOP program was utilized to design two sgRNAs targeting the UCA gene. sgRNA1 and sgRNA2 were inserted into two different CRISPR plasmids to produce two recombinant plasmids. These recombinant plasmids were simultaneously transfected into MCF-7 and MDA-MB 231 carcinoma of the breast cells. Proliferation and apoptosis were compared using the MTT test, CCK-8 assay, and flow cytometry evaluation. RNA-hybrid software, quantitative reverse transcription PCR, and luciferase assays were utilized to confirm the relationship between UCA1 and miR-143. Results: Proliferated cells were less active in MTT and CCK-8 tests and fellow cytometry analysis. The PX459-sgRNA1,2 group had elevated levels of the cancer biomarker Caspase-3 gene expression (P<0.001). When WT-UCA1 and miR-143 were co-transfected, the luciferase activity was drastically decreased. Conclusion: One very effective method of regulating cellular proliferation in vitro is the deletion of UCA1, which CRISPR/Cas9 accomplishes.

Treatment of chronic obstructive pulmonary disease by traditional Chinese medicine Morin monomer regulated by autophagy.

Background: Chronic obstructive pulmonary disease (COPD) is a frequently occurring disorder. The aim of this study is to explore the mechanism of traditional Chinese medicine Morin monomer in the treatment of COPD via regulating autophagy based on the long non-coding RNA (lncRNA) H19/microRNA (miR)-194-5p/Sirtuin (SIRT)1 signal axis. Methods: The COPD rat model was constructed, and the lung tissues were collected. The pathological analysis was performed using hematoxylin-eosin (HE), Masson, and periodic acid-Schiff (PAS) staining. Autophagosomes were observed using transmission electron microscope. LncRNA H19, miR-194-5p, SIRT1 genes in the rat lung tissues were detected using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). The autophagy-related proteins including SIRT1, mammalian/mechanistic target of rapamycin (mTOR), phosphorylated (p)-mTOR, microtubule-associated protein light chain 3 (LC3), Beclin-1, autophagy-related (ATG)7, and p62 in each group were detected using Western blot. Results: The rats in the control group had normal lung structure. Alveolar enlargement and destruction could be found in the rat lung tissues in the model group, accompanied with obvious infiltration of inflammatory cells, thickened bronchial walls, enlarged alveolar septum, collagen fibers deposition, and goblet cells proliferation. In comparison with the model group, Morin treatment relieved the lung injuries, which was optimized in the moderate- and high-dose groups. The number of autophagosomes in the lung tissues of the model rats was dramatically increased compared with the normal rats. However, the number of autophagosomes in each Morin treatment group was obviously less than that in the model group. LncRNA H19 and SIRT1 expression was significantly increased in the model group, and miR-194-5p was significantly decreased (P<0.05). Morin and 3-methyladenine (3-MA) could obviously reduce the lncRNA H19 and SIRT1 expression, and increase the miR-194-5p expression (P<0.05). Relative to control rats, ATG7, Beclin-1, LC3II/I and SIRT1 levels in the model group increased obviously, while the expression of p62, and p-mTOR/mTOR decreased (P<0.05). Morin treatment reduced the expression of ATG7, Beclin-1, SIRT1, LC3II/I significantly, and increased the p-mTOR/mTOR and p62 expression (P<0.05). Conclusions: Morin decreased lncRNA H19 expression, resulting in upregulation of miR-194-5p expression, downregulation of SIRT1 expression, and increased of p-mTOR/mTOR expression. Furthermore, cell autophagy was inhibited, contributing to the COPD treatment.

AAV vector-derived elements integrate into Cas9-generated double-strand breaks and disrupt gene transcription.

We previously developed an adeno-associated virus (AAV) Cas9 gene therapy for Angelman syndrome that integrated into the genome and prematurely terminated Ube3a-ATS. Here, we assessed the performance of 3 additional AAV vectors containing S. aureus Cas9 in vitro and in vivo, and 25 vectors containing N. meningitidis Cas9 in vitro, all targeting single sites within Ube3a-ATS. We found that none of these single-target gRNA vectors were as effective as multi-target gRNA vectors at reducing Ube3a-ATS expression in neurons. We also developed an anchored multiplex PCR sequencing method and analysis pipeline to quantify the relative frequency of all possible editing events at target sites, including AAV integration and unresolved double-strand breaks. We found that integration of AAV was the most frequent editing event (67%-89% of all edits) at three different single target sites, surpassing insertions and deletions (indels). None of the most frequently observed indels were capable of blocking transcription when incorporated into a Ube3a-ATS minigene reporter, whereas two vector derived elements-the poly(A) and reverse promoter-reduced downstream transcription by up to 50%. Our findings suggest that the probability that a gene trapping AAV integration event occurs is influenced by which vector-derived element(s) are integrated and by the number of target sites.

MIAT promotes myofibroblastic activities and transformation in oral submucous fibrosis through sponging the miR-342-3p/SOX6 axis.

Oral submucous fibrosis (OSF) is an oral potentially malignant disorder that is closely related to the habit of areca nut chewing. Long non-coding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) has been identified as an essential regulator in the fibrosis progression. However, the role of MIAT in the development of OSF remains unknown. The transcriptomic profile showed that MIAT is significantly overexpressed in the OSF cohort, with a positive correlation to fibrotic markers. The silencing of MIAT expression in primary buccal mucosal fibroblasts (BMFs) markedly inhibited arecoline-induced myofibroblast transformation. Mechanistically, MIAT functioned as a miR-342-3p sponge and suppressed the inhibitory effect of miR-342-3p on SOX6 mRNA, thereby reinstating SOX6 expression. Subsequent RNA expression rescue experiments confirmed that MIAT enhanced resistance to apoptosis and facilitated myofibroblastic properties such as cell mobility and collagen gel contraction by regulating the miR-342-3p/SOX6 axis. Taken together, these results suggest that the abnormal upregulation of MIAT is important in contributing persistent activation of myofibroblasts in fibrotic tissue, which may result from prolonged exposure to the constituents of areca nut. Furthermore, our findings demonstrated that therapeutic avenues that target the MIAT/miR-342-3p/SOX6 axis may be a promising approach for OSF treatments.

Non-Coding RNA as a Biomarker in Lung Cancer.

INTRODUCTION: Lung cancer remains one of the most prevalent and deadly cancers globally, with high mortality rates largely due to late-stage diagnosis, aggressive progression, and frequent recurrence. Despite advancements in diagnostic techniques and therapeutic interventions, the overall prognosis for lung cancer patients continues to be dismal. METHOD: Emerging research has identified non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs, and circular RNAs, as critical regulators of gene expression, significantly influencing cancer biology. These ncRNAs play pivotal roles in various aspects of lung cancer pathogenesis, including tumor initiation, progression, metastasis, and resistance to therapy. RESULTS: We provide a comprehensive analysis of the current understanding of ncRNAs in lung cancer, emphasizing their potential as biomarkers for early diagnosis, prognostication, and the prediction of the therapeutic response. We explore the biological functions of ncRNAs, their involvement in key oncogenic pathways, and the molecular mechanisms by which they modulate gene expression and cellular processes in lung cancer. Furthermore, this review highlights recent advances in ncRNA-based diagnostic tools and therapeutic strategies, such as miRNA mimics and inhibitors, lncRNA-targeted therapies, and circRNA-modulating approaches, offering promising avenues for personalized medicine. CONCLUSION: Finally, we discuss the challenges and future directions in ncRNA research, including the need for large-scale validation studies and the development of efficient delivery systems for ncRNA-based therapies. This review underscores the potential of ncRNAs to revolutionize lung cancer management by providing novel diagnostic and therapeutic options that could improve patient outcomes.

ANRIL regulates retinoblastoma progression via targeting autophagy by miR-328-3p/TSC1/ULK signaling.

Retinoblastoma is the most common primary intraocular malignancy of childhood. The aim of our study was to investigate the role and regulatory mechanism of the long non-coding RNA ANRIL in retinoblastoma. Here, our data demonstrated that ANRIL overexpression inhibited miR-328-3p expression, but promoted expression of autophagy-related proteins (LC3B, ATG5, and BECN1). Then we predicted the binding sites for ANRIL with miR-328-3p, and for miR-328 3p with TSC1/ULK2 3'-UTR, and confirmed the combination of miR-328-3p and ANRIL and TSC1/ULK2 3'-UTR. Importantly, the data showed that ANRIL overexpression promoted TSC1 and ULK2 expression, and inhibited the phosphorylation of mTOR. Finally, our results indicated that ANRIL overexpression facilitated Y79 cell proliferation and cisplatin-induced apoptosis. Our results indicated that ANRIL promoted the proliferation and cisplatin resistance of Y79 cells through activating autophagy by promoting TSC1/ULK2 ex- pression via acting as a miR-328-3p sponge.

The emerging modulators of non-coding RNAs in diabetic wound healing.

Diabetic wound healing is a complex physiological process often hindered by the underlying metabolic dysfunctions associated with diabetes. Despite existing treatments, there remains a critical need to explore innovative therapeutic strategies to improve patient outcomes. This article comprehensively examines the roles of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), in regulating key phases of the wound healing process: inflammation, angiogenesis, re-epithelialization, and tissue remodeling. Through a deep review of current literature, we discuss recent discoveries of ncRNAs that have been shown to either promote or impair the wound healing process in diabetic wound healing, which were not covered in earlier reviews. This review highlights the specific mechanisms by which these ncRNAs impact cellular behaviors and pathways critical to each healing stage. Our findings indicate that understanding these recently identified ncRNAs provides new insights into their potential roles in diabetic wound healing, thereby contributing valuable knowledge for future research directions in this field.

Identification and validation of an m7G-related lncRNAs signature for predicting prognosis, immune response and therapy landscapes in ovarian cancer.

Background: Ovarian cancer is the most mortality malignancy in gynecology. N7-methylguanosine (m7G) is one of the most prevalent RNA modifications in the development and progression of cancer. The aim of this study is to investigate the effect of m7G-related lncRNA on ovarian cancer in terms of instruction prognosis and immunotherapy. Methods: After integrating and processing the RNA expression profiles with the clinical sample information in the TCGA database, we initially screened to the m7G-related lncRNAs by Spearman correlation analysis, and subsequently obtained a prognostic model constructed by five m7G-related lncRNAs with Univariate Cox analysis, LASSO regression analysis, and Multivariate Cox regression analysis, after which we further evaluated and validated the prognostic value of the model using Kaplan-Meier survival analysis, Principal component analysis, Nomogram, and ROC curve. In addition, based on this risk model, we explored the differentially enriched pathways and functions of the high and low risk groups, and characterized the immune cells, immune functions, gene mutations, and drug sensitivity between the two groups. Results: After a series of rigorous filtering, we finally attained a prognostic risk model consisting of KRT7-AS, USP30-AS1, ZFHX4-AS1, ACAP2-IT1, and TWSG1-DT which is excellent in predicting the prognostic survival of ovarian cancer patients as well as existing as an independent prognostic factor. Moreover, the model has certain relevance in the immune cells and functions between high and low risk groups, and simultaneously, the signature has the role of guiding the option of immunotherapy and chemotherapeutic drugs. Conclusion: Altogether, our study established a tight connection between m7G-associated lncRNAs and ovarian cancer, with potential that the prognostic patterns contribute to steering the prognosis of ovarian cancer patients, measuring the efficacy of immunotherapeutic approaches, and detecting effective chemotherapeutic agents.

Dendritic cell-derived lncRNAs in patients with acute coronary syndrome.

Long non-coding RNAs (lncRNAs) and dendritic cells (DC) play crucial roles in the development of acute coronary syndrome (ACS); however, the mechanisms remain unclear. To investigate this, we analysed the differentially expressed lncRNAs in monocyte-derived DCs (moDCs) from patients with ACS. Peripheral blood mononuclear cells were transformed into moDCs. Cellular morphology and expression levels of moDC-specific markers (CD80, CD86, CD11c, CD14 and HLA-DR) were analysed using electron microscopy (EM) and flow cytometry (FCM), respectively. Differentially expressed lncRNAs and their functions were predicted using gene sequencing, gene ontology and the Kyoto Encyclopedia of Genes and Genomes. The expression levels of markers, signalling pathway molecules (p-PI3K and p-AKT), inflammatory cytokines (IL-6 and IL-12p70) and target gene (C-C motif chemokine ligand (CCL) 15 and CCL14) were analysed by overexpression or silencing of candidate lncRNAs. EM revealed the cells to be suspended in dendritic pseudopodia. CD11c and HLA-DR were upregulated, while CD80 and CD86 were downregulated. Comparison between the UA versus ST group showed the highest number of differentially expressed lncRNAs (n = 113), followed by UA versus NST (n = 115), CON versus NST (n = 49) and CON versus ST (n = 35); however, the number was low for CON versus UA and ST versus NST groups. moDC-specific marker expression, signalling pathway molecules, inflammatory cytokines and CCL14 were upregulated following lentiviral overexpression of smart silencer-CCL15-CCL14; however, expression levels decreased following transfection with siRNA. The morphology, function and lncRNA expression of moDCs differ depending on the type of ACS. The differentially expressed lncRNAs, particularly CCL15-CCL14, regulate the function of moDCs. Thus, our study provides new insights regarding the role of lncRNAs in ACS and indicates the potential use of CCL15-CCL14 as a novel diagnostic marker and therapeutic target.

CircRNA_SLC8A1 alleviates hypertrophic scar progression by mediating the Nrf2-ARE pathway.

BACKGROUND: Hypertrophic scar (HS) is associated with cosmetic defects, mobility, and functional impairments, pruritus, and pain. Previous circRNA microarray analysis identified reduced expression of circRNA_SLC8A1 in HS tissues. Therefore, this study aims to investigate the role of circRNA_SLC8A1 in modulating the abnormal behavior of HS-derived fibroblasts (HSFs) in vitro. METHODS: RT-qPCR and FISH assays were used to assess the differential expression and localization of circRNA_SLC8A1 in normal and HS tissues. Following modulation of circRNA_SLC8A1 expression, CCK-8, flow cytometry, Transwell, and wound healing assays were employed to evaluate the effects of circRNA_SLC8A1 on the biological behaviors of HSFs. The Starbase database, dual-luciferase reporter assays, and Ago2-RIP assays were utilized to predict and validate the interaction between circRNA_SLC8A1 and downstream miRNAs. RESULTS: CircRNA_SLC8A1 was found to be downregulated in HS tissues and was primarily localized in the cytoplasm. Overexpression of circRNA_SLC8A1 reduced cell viability, cell invasion, wound healing, and the expression of Vimentin, N-cadherin, Col I, and Col III, while enhancing apoptosis and E-cadherin expression in HSFs. CircRNA_SLC8A1 activates the Nrf2-ARE pathway by competitively binding to miRNA-27a-3p. miRNA-27a-3p and Nrf2 exhibited high and low expression, respectively in HS tissues, with an inverse correlation between their levels. Overexpression of miRNA-27a-3p counteracted the effects of circRNA_SLC8A1 in HSF proliferation, apoptosis, migration, EMT, collagen deposition, and Nrf2-ARE pathway activity. CONCLUSION: CircRNA_SLC8A1 inhibits the proliferation, migration, EMT, and collagen deposition of HSF through competitive binding with miRNA-27a-3p, thereby activating the Nrf2-ARE pathway. The circRNA_SLC8A1/miRNA-27a-3p/Nrf2-ARE axis may offer a promising molecular target for HS therapy.