Sepsis, a life-threatening syndrome, results from a dysregulated immune and hemostatic response, contributing to acute lung injury (ALI) and its progression into acute respiratory distress syndrome (ARDS). The development of septic ALI is complex, involving excessive inflammatory mediator production that damages endothelial and epithelial cells, leading to vascular leakage, edema, and vasodilation-key factors in ALI pathogenesis. Long noncoding RNAs (lncRNAs), over 200 nucleotides in length, play critical roles in various biological processes, including sepsis regulation. They exhibit both promotive and inhibitory effects, influencing sepsis progression and resolution. Despite their significance, comprehensive reviews detailing lncRNA involvement in sepsis-induced ALI remain limited. This review aims to address this gap by summarizing the diverse functions of lncRNAs in septic ALI, emphasizing their potential in diagnosis and treatment. Furthermore, we will explore the molecular mechanisms underlying lncRNA involvement, particularly their miRNA-dependent regulatory pathways. Understanding these interactions may provide novel insights into therapeutic strategies for sepsis-induced ALI.

Myostatin (Mstn) negatively regulates muscle growth and Mstn deficiency induced "double-skeletal muscle" development in vertebrates, including tilapias. In this study, we performed a transcriptomic analysis of skeletal muscle from both wild-type and mstnb-/- males to investigate the molecular mechanisms underlying skeletal muscle hypertrophy in mstnb-/- mutants. We identified 4697 differentially expressed genes (DEGs), 113 differentially expressed long non-coding RNAs (DE lncRNAs), 211 differentially expressed circular RNAs (DE circRNAs), and 98 differentially expressed microRNAs (DE miRNAs). The DEGs were significantly enriched in proteasome and ubiquitin-mediated proteolysis pathways. Cis- and trans-targeting genes of DE lncRNAs were also notably enriched in the above two pathways. The putative host genes of DE circRNAs linked to myofibrils, contractile fibers, and so on. Additionally, DE miRNAs were associated with ubiquitin-mediated proteolysis and key signaling pathways, including AMPK, FoxO, and mTOR. Furthermore, the core competing endogenous RNA (ceRNA) network was constructed comprising 31 DEGs, 37 DE miRNAs, 14 DE circRNAs, and 45 DE lncRNAs. The key roles of ubiquitin-proteasome system were highlighted in the ceRNA network. Taken together, this study provides a novel perspective on muscle mass increase in Mstn mutants through the repression of protein degradation and facilitates our understanding of the molecular mechanisms of skeletal muscle hypertrophy in fish.

Epstein-Barr virus (EBV) employs various strategies for long-term survival, including the expression of non-coding RNAs (ncRNAs). This study uncovers and characterizes two novel EBV-encoded ncRNAs, p7 and p8, which are upregulated during lytic reactivation and interact with both viral and host genomes. These ncRNAs bind to cellular RNA transcripts, significantly reducing ARMCX3 mRNA levels, while p8 also influences PTPN6 and RPL24 expressions. Although p7 does not directly bind to LMP1 RNA but both ncRNAs found to downregulate LMP1 expression. Furthermore, these ncRNAs interact with the OriLyt region of EBV genome, promoting viral DNA replication. Functional assays indicate that p7 and p8 enhance cell proliferation and inhibit apoptosis by modulating the p53 pathway and suppressing pro-apoptotic proteins. These findings highlight the role of p7 and p8 in supporting EBV persistence by regulating viral replication, cell survival, and immune evasion, making them promising targets for therapeutic strategies in EBV-related diseases.IMPORTANCEEpstein-Barr virus (EBV) employs diverse strategies for long-term persistence in the host, including the expression of viral non-coding RNAs (ncRNAs) that manipulate key cellular pathways to promote viral replication and immune evasion. This study identifies two novel EBV-encoded ncRNAs, p7 and p8, which are upregulated during lytic reactivation and interact with both viral and host genes to regulate viral DNA replication and promote host cellular survival. By modulating apoptotic and proliferative pathways, p7 and p8 facilitate viral reactivation while promoting host cell survival, highlighting their potential as critical regulators in EBV-driven oncogenesis. This discovery expands our understanding of EBV-host interactions, suggesting p7 and p8 as targets for novel therapeutic strategies in EBV-associated malignancies.

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 (4 weeks), 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 4 weeks 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.

Accumulation of calcium phosphate crystals is associated with vascular calcification (VC); however, the mechanism that promotes VC remains unclear. Accumulating evidence indicates that smooth muscle and endothelial cell-enriched migration/differentiation-associated lncRNA (SENCR) exerts a critical role in VC. This work focuses on the molecules involved in β-glycerophosphate-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through SENCR epigenetic modification of Runx2 in an endoplasmic reticulum stress (ERS)-dependent manner.

We cultured VSMCs to explore the relationship among β-glycerophosphate, SENCR, and VC and also investigate the function of SENCR in β-glycerophosphate-induced osteogenic differentiation and VC in vitro.

Our findings indicate that β-glycerophosphate enhanced SENCR, MSH homeobox 2, Runx2, ERS-related markers, alkaline phosphatase activity, and cellular calcium deposition and suppressed the expression of α-SMA, SM 22α, and miR-4731-5p. SENCR silencing increased miR-4731-5p expression, which subsequently inhibited β-glycerophosphate-associated endoplasmic reticulum stress at the post-transcriptional level. Critically, the facts that direct interplay between SENCR and miR-4731-5p, and the downregulation of miR-4731-5p efficiently reversed the suppression of ERS-induced by SENCR silencing were observed. Collectively, the present study clarifies a novel mechanism by which downregulation of SRNRC contributes to the ERS-dependent osteogenic differentiation of VSMCs and VC by sponging miR-4731-5p. This study demonstrates that SENCR/miR-4731-5p axis is involved in β-glycerophosphate-mediated VC in vitro.

RNAs play critical roles in most biological processes. Although the three-dimensional (3D) structures of RNAs primarily determine their functions, it remains challenging to experimentally determine these 3D structures due to their conformational heterogeneity and intrinsic dynamics. Cryogenic electron microscopy (cryo-EM) has recently played an emerging role in resolving dynamic conformational changes and understanding structure-function relationships of RNAs including ribozymes, riboswitches and bacterial and viral noncoding RNAs. A variety of methods and pipelines have been developed to facilitate cryo-EM structure determination of challenging RNA targets with small molecular weights at subnanometer to near-atomic resolutions. While a wide range of conditions have been used to prepare RNAs for cryo-EM analysis, correlations between the variables in these conditions and cryo-EM visualizations and reconstructions remain underexplored, which continue to hinder optimizations of RNA samples for high-resolution cryo-EM structure determination. Here we present a protocol that describes rigorous screenings and iterative optimizations of RNA preparation conditions that facilitate cryo-EM structure determination, supplemented by cryo-EM data processing pipelines that resolve RNA dynamics and conformational changes and RNA modeling algorithms that generate atomic coordinates based on moderate- to high-resolution cryo-EM density maps. The current protocol is designed for users with basic skills and experience in RNA biochemistry, cryo-EM and RNA modeling. The expected time to carry out this protocol may range from 3 days to more than 3 weeks, depending on the many variables described in the protocol. For particularly challenging RNA targets, this protocol could also serve as a starting point for further optimizations.

LINC00926 has been identified as an upregulated lncRNA in patients with coronary heart disease (CHD) through high-throughput sequencing. This study aimed to explore the biological role of LINC00926 in vascular endothelial cell ferroptosis and its underlying mechanisms. For in vitro experiments, HUVECs were exposed to hypoxic conditions. Our results showed an upregulation of LINC00926 expression, a decrease in GPX4 and GSH levels, and an increase in MDA and ROS levels in hypoxia-treated HUVECs. Furthermore, the ferroptosis inhibitor (ferrostatin-1) reversed the decrease in cell viability induced by hypoxia, suggesting that hypoxia treatment triggered GPX4-mediated ferroptosis in HUVECs. These variations were further exacerbated when LINC00926 was overexpressed, but were partially mitigated when LINC00926 was silenced. Notably, LINC00926 had no effect on GPX4 mRNA levels. Our data proved that LINC00926 modulated the ubiquitination and degradation of GPX4 via STUB1, thereby promoting hypoxia-induced HUVEC ferroptosis. Additionally, ChIP and luciferase reporter gene assays confirmed that TCF12 protein enhanced the transcriptional activity of LINC00926 promoter, hinting TCF12 is an upstream regulator of LINC00926. Besides, LINC00926 also enhanced the stability of TCF12 mRNA to promote TCF12 expression. Moreover, TCF12 acted as a regulator of ferroptosis in hypoxia-induced HUVECs. Finally, rescue experiments determined the role of the TCF12/LINC00926/GPX4 axis in ferroptosis of HUVECs upon hypoxic stimulation. In conclusion, this study demonstrated that the TCF12/LINC00926/GPX4 axis plays a regulatory role in hypoxia-induced ferroptosis of HUVECs, offering a promising target for the treatment of CHD.

Colorectal cancer (CRC) remains one of the leading causes of cancer-related death worldwide. The precursor of CRC is a colorectal polyp, of which adenoma is the most common histological type. The initial step in CRC development is the gradual accumulation of a series of genetic and epigenetic alterations in the normal colonic epithelium. Genetic alterations play a major role in a subset of CRCs, but the pathophysiological contribution of epigenetic aberrations has recently attracted attention. Epigenetic marks occur early in cancer pathogenesis and are therefore important molecular hallmarks of cancer. This makes some epigenetic alterations clinically relevant for early detection not only of CRC but also of precancerous polyps. In this review we focus on three types of non-coding RNAs as epigenetic regulators: miRNA, lncRNA, and lncRNAs, highlighting their biomarker potential.

The urokinase-receptor (uPAR) exerts multiple functions supporting most cancer hallmarks. Increased uPAR expression is associated with an unfavorable prognosis in several cancer types, including hematologic malignancies. We previously reported that three oncosuppressor microRNAs (miRNAs) can target the 3'untranslated region (3'UTR) of the uPAR mRNA and that uPAR mRNA is a competitive endogenous RNA (ceRNA) able to recruit oncosuppressor miRs, thus impairing their activity. We now show that uPAR mRNA can also be targeted by oncosuppressor members of the let-7 miRNA family in acute myeloid leukemia (AML) cell lines. Indeed, let-7a, let7d and let-7g directly target the 3'UTR of uPAR mRNA, thus down-regulating uPAR expression. These let-7 miRNAs are expressed in KG1 and U937 AML cells; their levels are high in KG1 cells, which express low uPAR levels, and low in the U937 cell line, expressing high levels of uPAR. Overexpression of these miRNAs down-regulates uPAR expression and impairs the adhesion to fibronectin and migration of U937 cells, without affecting their proliferation. Accordingly, the overexpression of specific inhibitors targeting these let-7 miRNAs efficiently increases uPAR expression in KG1 cells. These results indicate that selected let-7 miRNAs regulate uPAR expression and impair the adhesion and migration of AML cells.

Muscle fibers, as the fundamental units of muscle tissue, play a crucial role in determining skeletal muscle function through their growth, development, and composition. To investigate changes in muscle fiber types and their regulatory mechanisms in Mongolian horses (MG), Xilingol horses (XL), and Grassland-Thoroughbreds (CY), we conducted histological and bioinformatic analyses on the gluteus medius muscle of these three horse breeds. Immunofluorescence analysis revealed that Grassland-Thoroughbreds had the highest proportion of fast-twitch muscle fibers at 78.63%, while Mongolian horses had the lowest proportion at 57.54%. Whole-transcriptome analysis identified 105 differentially expressed genes (DEGs) in the CY vs. MG comparison and 104 DEGs in the CY vs. XL comparison. Time-series expression profiling grouped the DEGs into eight gene sets, with three sets showing significantly up-regulated or down-regulated expression patterns (p < 0.05). Additionally, 280 differentially expressed long non-coding RNAs (DELs) were identified in CY vs. MG, and 213 DELs were identified in CY vs. XL. A total of 32 differentially expressed microRNAs (DEMIRs) were identified in CY vs. MG, while 44 DEMIRs were found in CY vs. XL. Functional enrichment analysis indicated that the DEGs were significantly enriched in essential biological processes, such as actin filament organization, muscle contraction, and protein phosphorylation. KEGG pathway analysis showed their involvement in key signaling pathways, including the mTOR signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. Furthermore, functional variation-based analyses revealed associations between non-coding RNAs and mRNAs, with some non-coding RNAs targeting genes potentially related to muscle function regulation. These findings provide valuable insights into the molecular basis for the environmental adaptability, athletic performance, and muscle characteristics in horses, offering new perspectives for the breeding of Grassland-Thoroughbreds.

Osteoarthritis (OA) is a chronic joint disease characterized by articular cartilage degeneration and damage. Increasing circular RNAs (circRNAs) have been identified to participate in the pathogenesis of OA. Hsa_circ_0128006 (also known as circSEC24) was reported as an upregulated circRNA in OA tissues, but its biological role and underlying mechanism in OA are still to be discussed. circSEC24A and NAMPT expression levels were upregulated, and miR-515-5p was reduced in OA cartilage tissues and IL-1β-treated CHON-001 cells. The absence of circSEC24A overturned IL-1β-induced suppression of cell viability and promotion of oxidative stress, apoptosis, extracellular matrix (ECM) degradation, and inflammation in CHON-001 cells. Mechanistically, circSEC24A acted as a molecular sponge for miR-515-5p to affect NAMPT expression. CircSEC24A knockdown could attenuate IL-1β-triggered CHON-001 cell injury partly via the miR-515-5p/NAMPT axis, providing new insight into the underlying application of circSEC24A in OA treatment.

The centrosome is the microtubule-organizing center and a crucial part of cell division. Centrosomal RNAs (cnRNAs) have been reported to enable precise spatiotemporal control of gene expression during cell division in many species. Whether and how cnRNAs exist in C. elegans are unclear. Here, using the nuclear RNAi Argonaute protein NRDE-3 as a reporter, we observed potential peri-centrosome localized small interfering (si)RNAs in C. elegans. NRDE-3 was previously shown to associate with pre-mRNAs and pre-rRNAs via a process involving the presence of complementary siRNAs. We generated a GFP-NRDE-3 knock-in transgene through CRISPR/Cas9 technology and observed that NRDE-3 formed peri-centrosomal foci neighboring the tubulin protein TBB-2, other centriole proteins and pericentriolar material (PCM) components in C. elegans embryos. The peri-centrosomal accumulation of NRDE-3 depends on RNA-dependent RNA polymerase (RdRP)-synthesized 22G siRNAs and the PAZ domain of NRDE-3, which is essential for siRNA binding. Mutation of eri-1, ergo-1, or drh-3 significantly increased the percentage of pericentrosome-enriched NRDE-3. At the metaphase of the cell cycle, NRDE-3 was enriched in both the peri-centrosomal region and the spindle. Moreover, the integrity of centriole proteins and pericentriolar material (PCM) components is also required for the peri-centrosomal accumulation of NRDE-3. Therefore, we concluded that siRNAs could accumulate in the pericentrosomal region in C. elegans and suggested that the peri-centrosomal region may also be a platform for RNAi-mediated gene regulation.

Our study investigates gene expression in adipose tissue of Ames dwarf (df/df) mice, whose deficiency in growth hormone is linked to health and extended lifespan. Recognizing adipose tissue influence on metabolism, aging, and related diseases, we aim to understand its contribution to the health and longevity of df/df mice. We have identified gene and transcript expression patterns associated with critical biological functions, including metabolism, stress response, and resistance to cancer. Intriguingly, we identified genes that, despite maintaining unchanged expression levels, switch between different isoforms, impacting essential cellular functions such as tumor suppression, oncogenic activity, ATP transport, and lipid biosynthesis and storage. The isoform switching is associated with changes in protein domains, retention of introns, initiation of nonsense-mediated decay, and emergence of intrinsically disordered regions. Moreover, we detected various alternative splicing events that may drive these structural alterations. We also found changes in the expression of long non-coding RNAs (lncRNAs) that may be involved in the aging process and disease resistance by regulating crucial genes in survival and metabolism. Through weighted gene co-expression network analysis, we have linked four lncRNAs with 29 genes, which contribute to protein complexes such as the Mili-Tdrd1-Tdrd12 complex. Beyond safeguarding DNA integrity, this complex also has a wider impact on gene regulation, chromatin structure, and metabolic control. Our detailed investigation provides insight into the molecular foundations of the remarkable health and longevity of df/df mice, emphasizing the significance of adipose tissue in aging and identifying new avenues for health-promoting therapeutic strategies.

Despite the frequent implication of aberrant gene expression in diseases, algorithms predicting aberrantly expressed genes of an individual are lacking. To address this need, we compile an aberrant expression prediction benchmark covering 8.2 million rare variants from 633 individuals across 49 tissues. While not geared toward aberrant expression, the deleteriousness score CADD and the loss-of-function predictor LOFTEE show mild predictive ability (1-1.6% average precision). Leveraging these and further variant annotations, we next train AbExp, a model that yields 12% average precision by combining in a tissue-specific fashion expression variability with variant effects on isoforms and on aberrant splicing. Integrating expression measurements from clinically accessible tissues leads to another two-fold improvement. Furthermore, we show on UK Biobank blood traits that performing rare variant association testing using the continuous and tissue-specific AbExp variant scores instead of LOFTEE variant burden increases gene discovery sensitivity and enables improved phenotype predictions.

The pathogenesis of cartilage injury and degeneration is exceptionally complex. In addition to being associated with osteoarthritis and trauma, factors such as age, gender, obesity, inflammation, and apoptosis of chondrocytes are also considered significant influencing factors. Due to the lack of direct blood supply, lymphatic circulation, and neural innervation, coupled with low metabolic activity, the self-repair capability of cartilage after injury is extremely limited, making its treatment quite challenging. Recent research indicated that ncRNA, a class of RNA transcribed from the genome that does not encode proteins, played a crucial regulatory role in various disease processes. Particularly noteworthy is its positive regulatory role in cartilage regeneration, achieved through the modulation of the inflammatory microenvironment, promotion of chondrocyte proliferation, inhibition of chondrocyte degradation, and facilitation of the recruitment and differentiation of bone marrow mesenchymal stem cells into chondrocytes. In the earlier phase, we conducted a review and outlook on therapeutic strategies for the regeneration of articular cartilage injuries. This article specifically focuses on summarizing the regulatory roles and research advancements of ncRNA in cartilage regeneration, as well as its contributions to the clinical application of gene therapy for cartilage defects.

Despite significant advancements in early detection and treatment, non-small-cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. Specifically, in early-stage cases, recurrence after surgery continues to be the principal cause of death for these patients. The urgent need for novel diagnostic and prognostic biomarkers has directed attention towards PIWI-interacting RNAs (piRNAs), a group of small RNAs that regulate genomic stability and epigenetics. Some piRNAs, including hsa_piR_022710, hsa_piR_019822, and hsa_piR_020840, have been described as deregulated in various cancers. This study investigated the expression of these three piRNAs by RT-qPCR in 277 NSCLC patients and developed survival and CART classification models to predict recurrence risk, overall survival (OS), and disease-free survival (DFS). hsa_piR_019822 and hsa_piR_020840 were able to discriminate between tumor and normal tissue, as well as between adenocarcinoma and squamous cell carcinoma (LUSC) patients. Elevated expression of hsa_piR_019822 and hsa_piR_022710 was correlated with an increased risk of recurrence and poorer DFS and OS in LUSC patients. Patients with high hsa_piR_022710 expression more greatly benefited from adjuvant treatment. In summary, higher piRNA levels were associated with an increased risk of recurrence and poorer survival outcomes, especially in LUSC patients, where they may help guide personalized treatment strategies.

Early diagnosis of lung cancer (LC) is challenging, treatment options are limited, and treatment resistance leads to poor prognosis and management in most patients. The Wnt/β-catenin signaling pathway plays a vital role in the occurrence, progression, and therapeutic response of LC. Recent studies indicate that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) function as epigenetic regulators that can promote or inhibit Wnt/β-catenin signaling by interacting with Wnt proteins, receptors, signaling transducers, and transcriptional effectors, thereby affecting LC cell proliferation, metastasis, invasion, and treatment resistance. Deepening our understanding of the regulatory network between ncRNAs and the Wnt/β-catenin signaling pathway will help overcome the limitations of current LC diagnosis and treatment methods. This article comprehensively reviews the regulatory mechanisms related to the functions of ncRNAs and the Wnt/β-catenin pathway in LC, examining their potential as diagnostic and prognostic biomarkers and therapeutic targets, aiming to offer new promising perspectives for LC diagnosis and treatment.

Glioblastoma (GBM) is an aggressive malignant brain tumor with almost inevitable recurrence despite multimodal management with surgical resection and radio-chemotherapy. While several genetic, proteomic, cellular, and anatomic factors interplay to drive recurrence and promote treatment resistance, the epigenetic component remains among the most versatile and heterogeneous of these factors. Herein, the epigenetic landscape of GBM refers to a myriad of modifications and processes that can alter gene expression without altering the genetic code of cancer cells. These processes encompass DNA methylation, histone modification, chromatin remodeling, and non-coding RNA molecules, all of which have been found to be implicated in augmenting the tumor's aggressive behavior and driving its resistance to therapeutics. This review aims to delve into the underlying interactions that mediate this role for each of these epigenetic components. Further, it discusses the two-way relationship between epigenetic modifications and tumor heterogeneity and plasticity, which are crucial to effectively treat GBM. Finally, we build on the previous characterization of epigenetic modifications and interactions to explore specific targets that have been investigated for the development of promising therapeutic agents.

RNA interference through small interfering RNA (siRNA) has shown great promise as a potential cancer treatment strategy in recent years. However, the delivery of siRNA to target cancer cells efficiently remains a significant challenge. This review aims to highlight the recent advances in nanotechnology-enabled siRNA delivery for cancer treatment, bridging the gap between bench research and clinical application. A comprehensive literature search was conducted to identify recent studies focused on the utilization of nanotechnology for siRNA delivery in cancer treatment. Key databases, including PubMed, Scopus, and Web of Science, were used, and relevant articles were screened. Several nanotechnology-based platforms for siRNA delivery have emerged in recent years, providing enhanced selectivity, improved stability, and controlled release profiles. The primary types of nanocarriers discussed include lipid-based nanoparticles, inorganic nanoparticles, polymeric nanoparticles, and exosomes. Nanotechnology-based siRNA delivery systems represent a promising avenue for cancer treatment. Although significant progress has been made in preclinical studies, translating these findings to clinical applications poses several challenges, including scale-up production, safety, and targeted delivery. Nevertheless, the recent developments in this field hold great promise in revolutionizing cancer therapy, providing hope for more effective and personalized treatment options in the future.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic inflammatory responses in the joints, synovial hyperplasia, persistent abnormal proliferation of fibroblast-like synoviocytes (FLSs), and cartilage erosion, leading to joint swelling and destruction. The underlying mechanisms of this disease entail a complex interplay of factors, with long noncoding RNAs (lncRNAs) serving as the main contributors. These lncRNAs, which are over 200 bp in length, are involved in regulating inflammatory responses, joint damage, and FLS growth. Studies have shown that lncRNAs have a dual function in the progression of RA, as they can both promote the disease and control inflammatory responses to reduce symptoms. Nevertheless, our current understanding of the dual function of lncRNAs in the development of RA is incomplete, and the exact molecular mechanisms involved in this process remain unclear. This study aims to elucidate the molecular mechanisms by which lncRNAs exert their inhibitory and stimulatory effects, as well as explore the potential of lncRNAs in diagnosing, predicting the prognosis, and targeting therapy for RA.

Noncoding RNAs (ncRNAs) have emerged as pivotal regulators of gene expression, and have attracted significant attention because of their various roles in biological processes. These molecules have transcriptional activity despite their inability to encode proteins. Moreover, research has revealed that ncRNAs, especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are linked to pervasive regulators of kidney disease, including anti-inflammatory, antiapoptotic, antifibrotic, and proangiogenic actions in acute and chronic kidney disease. Although the exact therapeutic mechanism of ncRNAs remains uncertain, their value in treatment has been studied in clinical trials. The numerous renal diseases and the beneficial or harmful effects of NcRNAs on the kidney will be discussed in this article. Afterward, exploring the biological characteristics of ncRNAs, as well as their purpose and potential contributions to acute and chronic renal disease, were explored. This may offer guidance for treating both acute and long-term kidney illnesses, as well as insights into the potential use of these indicators as kidney disease biomarkers.

Acute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, often associated with severe complications and even death. In ALI, macrophages, alveolar epithelial cells and vascular endothelial cells in the lung are damaged to varying degrees and their function is impaired. Research in recent years has focused on the use of SIRT1 for the treatment of ALI. In this paper, we reviewed the role of SIRT1 in ALI in terms of its cellular and molecular mechanism, targeting of SIRT1 by non-coding RNAs and drug components, as well as pointing out the value of SIRT1 for clinical diagnosis and prognosis. Based on the current literature, SIRT1 exhibits diverse functionalities and possesses significant therapeutic potential. Targeting SIRT1 may provide new therapeutic ideas for the treatment of ALI.

Current endometrial receptivity analysis is invasive, preventing embryo transfer during the biopsy cycle. This study aims to screen serum sncRNAs as non-invasive biomarkers for ERA tests.

The study included 12 infertile patients undergoing IVF-ET and ERA, whose serum samples were collected for high-energy sequencing technology to detect sncRNA expression profiles. We overexpressed and knocked down tsRNA-35:73-Asp-GTC-1 in the decidualized Immortalized Human Eutopic Endometrial Stromal Cells (HESC) model cultured in vitro to further investigate the its effect on decidualization. The predicted tsRNA-35:73-Asp-GTC-1 target gene was verified by PCR analysis.

We screened 286 differentially expressed tsRNAs, 46 miRNAs, and 106 piRNAs. KEGG analysis indicated that differentially expressed tsRNAs were associated with pathways such as 'Calcium signaling pathway,' 'Sphingolipid signaling pathway,' etc. The results of RT-qPCR validation showed that the trends of four significantly differentially expressed tsRNAs in serum and endometrium were consistent with sequencing results. ROC curves demonstrated that these four tsRNAs have good predictive value for endometrial receptivity. Overexpression of tsRNA-35:73-Asp-GTC-1 affected the morphology of decidualized cells, and the decidualization indicators also showed a decreasing trend. While knocking down tsRNA-35:73-Asp-GTC-1 had the opposite effect. The RT-qPCR results showed that tsRNA-35:73-Asp-GTC-1 was associated with the Wnt3 target gene.

Serum sncRNA analysis shows potential for studying the molecular mechanisms of endometrial receptivity. Four serum tsRNAs can serve as novel biomarkers for non-invasive endometrial receptivity detection. TsRNA-35:73-Asp-GTC-1 may further regulate endometrial receptivity by targeting Wnt3.

Transcription takes place over a significant portion of the human genome. However, only a small portion of the transcriptome, roughly 1.2 %, consists of RNAs translated into proteins; the majority of transcripts, on the other hand, comprise a variety of RNA families with varying sizes and functions. A substantial portion of this diverse RNA universe consists of sequences longer than 200 bases, called the long non-coding RNA (lncRNA). The control of gene transcription, changes to DNA topology, nucleosome organization and structure, paraspeckle creation, and assistance for developing cellular organelles are only a few of the numerous tasks performed by lncRNA. The main focus of this study is on the function of lncRNA in controlling the levels and actions of cyclin-dependent kinase inhibitors (CDKIs). The enzymes required for the mitotic cycle's regulated progression are called cyclin-dependent kinases (CDKs). They have many degrees of regulation over their activities and interact with CDKIs as their crucial mechanisms. Interestingly, culminating evidence has clarified that lncRNAs are associated with several illnesses and use CDKI regulation to control cellular function. Nonetheless, despite the abundance of solid evidence in the literature, it still seems unlikely that lncRNA will have much of an impact on controlling cell proliferation or modulating CDKIs.

Echoes of natural and anthropogenic stressors not only reverberate within the physiology, biology, and neurobiology of the generation directly exposed to them but also within the biology of future generations. With the intent of understanding this phenomenon, significant efforts have been made to establish how exposure to psychosocial stress, chemicals, over- and undernutrition, and chemosensory experiences exert multigenerational influences. From these studies, we are gaining new appreciation for how negative environmental events experienced by one generation impact future generations. In this review, we first outline the need to operationally define dimensions of negative environmental events in the laboratory and the routes by which the impact of such events are felt through generations. Next, we discuss molecular processes that cause the effects of negative environmental events to be initiated in the exposed generation and then perpetuated across generations. Finally, we discuss how legacies of flourishing can be engineered to halt or reverse multigenerational influences of negative environmental events. In summary, this review synthesizes our current understanding of the concept, causes, and consequences of multigenerational echoes of stress and looks for opportunities to halt them.

As emerging biomaterials, framework nucleic acids (FNAs) have recently demonstrated great potential in the biomedical field due to their high programmability, biocompatibility, unique structural diversity, and precise molecular design capabilities. This review focuses on the applications of FNAs in cellular sensing and disease treatment. First, we systematically introduce the applications of FNAs in cellular sensing, including their precise recognition and response to the extracellular tumor microenvironment, cell membrane proteins, and intracellular biomarkers. Subsequently, we review the potential of FNAs in disease treatment, covering their applications and development in drug delivery, regulation of cell behavior, and immunomodulation. We also discuss the limitations and potential role of FNAs in personalized medicine, precision diagnostics, and advanced therapies. The broad application of FNAs is expected to drive significant breakthroughs in future biomedical technological innovations and clinical translation.

The exact mechanisms and key functional molecules involved in skin ageing remain largely unknown. Studies linking the expression of messenger RNAs (mRNAs) and small noncoding RNAs (sncRNAs) to skin ageing are limited. In this study, we performed RNA sequencing to assess the effects of ageing on the expression of mRNAs and sncRNAs in rat skin. Our results revealed that 241 mRNAs, 109 microRNAs (miRNAs), 20 piwi-interacting RNAs (piRNAs), 45 small nucleolar RNAs (snoRNAs), and 7 small nuclear RNAs (snRNAs) were significantly differentially expressed in the skin of aged rats compared to their younger counterparts. Histological validation using RT-qPCR further verified the significant differential expression of 13 mRNAs, 7 miRNAs, 2 piRNAs, 15 snoRNAs, and 1 snRNA. Additionally, several sncRNAs showed differential expression across various tissues, suggesting that they may have broad correlations with ageing. After establishing cellular senescence in skin fibroblasts, we identified 4 mRNAs, 4 miRNAs, and 10 snoRNAs that may mediate skin ageing by modulating fibroblast senescence. Notably, overexpression or knockdown of some differentially expressed RNAs in fibroblasts influenced cellular senescence, indicating that these RNAs could play an important role in the skin ageing process. These findings highlight their potential significance for future treatments of age-related skin disorders.

Non-coding small molecule RNAs are associated with a variety of diseases, including infectious diseases. However, small RNA-related studies in onychomycosis have not been reported. The aim of the present study was to conduct an initial investigation of small RNA in onychomycosis. The present study collected a total of 33 affected nail samples from patients with onychomycosis and 18 normal nail samples from healthy people. Through RNA sequencing, 37 differentially expressed microRNAs (miRNAs or miRs), including 15 upregulated and 22 downregulated miRNAs, were identified in 3 patients with onychomycosis compared with 3 healthy controls. Moreover, three differentially expressed miRNAs were analyzed for further verification by RT-qPCR in other 30 affected nail and 15 healthy nail samples. Among the three verified miRNAs, a significant difference between the downregulated hsa-miR-1-3p and hsa-miR-361-3p was observed (P<0.05). A total of 14,511 target genes of 37 differentially expressed miRNAs were predicted by the miRanda and RNAhybrid databases, while the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis showed that these target genes were enriched in multiple signaling pathways. The present study indicated that hsa-miR-1-3p and hsa-miR-361-3p may be potential biomarkers for onychomycosis. Furthermore, the findings of the present study can be used in future research on RNA in onychomycosis.

Recent studies have found Several lncRNAs were proved differential expression in diminished ovarian reserve (DOR) patients, however, the mechanism of DOR caused by lncRNAs is still largely unclear.

High throughput sequencing was performed in ovarian GCs extracted from women with normal ovarian function and women with DOR. Bioinformation analysis was used to analyze the sequencing data and identify the differential expression of lncRNAs. Quantitative RT-PCR (qRT-PCR) was used to verify the sequencing results. Situ fluorescence hybridization (FISH) followed by confocal microscopy and qRT-PCR were used to explore the location and expression of LncRNA-THBS4 in GCs. The significantly enriched signaling pathways of LncRNA-THBS4 were identified by KEGG. The study used RNA interference technology to decipher LncRNA-THBS4 function by silencing LncRNA-THBS4 in GCs. Western blot and qRT-PCR were used to explore the mRNA and protein expressions of key factors of PI3Ks pathway. The pro-apoptotic protein and anti-apoptotic protein were detected by western blot. The proliferation and apoptosis of GCs were detected by MTT assay and Flow cytometry.

197 lncRNAs with significant differences in expression levels were detected between control and DOR group by high throughput sequencing. The study found the expression of LncRNA-THBS4 in GCs was positively correlated with Anti-Mullerian hormone (AMH) (p = 0.0020, r = 0.4742)、antral follicle count (AFC) (p = 0.0007, r = 0.5130)、good embryo rate (p = 0.0006, r = 0.5210), negatively correlated with basal FSH level (p = 0.0007, r = －0.5152). LncRNA-THBS4 was mainly localized in the cytoplasm of GCs. LncRNA-THBS4 silencing could inhibit the PI3Ks pathway; decrease the levels of anti-apoptotic protein, inhibit the proliferation of GCs; increase the levels of apoptosis protein, enhance the apoptosis of GCs.

The expression level of lncRNA-THBS4 is correlated with ovarian function indicators and pregnancy outcomes in women. LncRNA-THBS4 may participate in the pathogenesis of DOR by affecting the proliferation and apoptosis of GCs via regulating PI3K/AKT/mTOR signaling pathway.

Infertility is a widespread clinical problem that affects human reproduction and species persistence worldwide. Around 40-70% of cases are due to male reproductive defects. Functional spermatogenesis (sperm production through several coordinated events) is at the heart of male fertility. Non-coding RNAs (ncRNAs) are the primary regulators of gene expression, controlling extensive critical cellular processes, for example proliferation, differentiation, apoptosis, and reproduction. Due to advancements in high-throughput sequencing tools, many studies have revealed that ncRNAs are widely expressed in germ cells, meiosis, spermatogenesis, sperm fertility, early post-fertilization development, and male infertility. The present review examines the biology and function of ncRNAs, including microRNAs, circular RNAs, and long ncRNAs, in spermatogenesis, their correlation with infertility, and their potential as biomarkers for sperm quality and fertility. The function of ncRNA in Sertoli cells (SCs) and Leydig cells (LCs) is also outlined throughout this study, because spermatogenesis requires testicular somatic cells to be involved in testicular development and male fertility. Meanwhile, the future development of ncRNAs for the clinical treatment of male infertility is also anticipated and discussed.

Cancer immunotherapy has shown significant potential in treating several malignancies by stimulating the host immune system to recognize and attack cancer cells. Immunogenic cell death (ICD) can amplify the antitumor immune responses and reverse the immunosuppressive tumor microenvironment, thus increasing the sensitivity of cancer immunotherapy. In recent years, noncoding RNAs (ncRNAs) have emerged as key regulatory factors in ICD and oncologic immunity. Accordingly, ICD-related ncRNAs hold promise as novel therapeutic targets for optimizing the efficacy of cancer immunotherapy. However, the immunomodulatory properties of ICD-related ncRNAs have not yet been comprehensively summarized. Hence, we summarize the current knowledge on ncRNAs involved in ICD and their potential roles in cancer immunotherapy in this review. It deepens our understanding of ncRNAs associated with ICD and provides a new strategy to enhance cancer immunotherapy by specifically targeting the ICD-related ncRNAs.

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulatory molecules in cancer biology. Among these, long intergenic non-protein coding RNA 02418 (LINC02418), a recently identified lncRNA, has been linked to endometrial cancer (EC), although its function and operational mechanisms are largely unclear. The present investigation aims to elucidate the molecular mechanism through which LINC02418 influences EC pathogenesis. We employed Western blotting and quantitative real-time PCR to analyze Ras protein specific guanine nucleotide releasing factor 1 (RASGRF1) and LINC02418 expression profiles in EC tissues and cell lines. Functional analyses, including cell proliferation, migration, and invasion assays, were conducted to evaluate the impact of LINC02418 overexpression on EC cells. Xenograft mouse models were established for in vivo validation. The molecular interactions between LINC02418, miR-494-3p, and RASGRF1 were characterized using luciferase reporter and RNA pull-down assays. LINC02418 expression was significantly downregulated in EC tissues and cell lines compared to their normal counterparts. Forced expression of LINC02418 significantly suppressed EC cell proliferation, migration, and invasion in vitro. In xenograft models, LINC02418 overexpression resulted in reduced tumor burden and enhanced cell death. Mechanistically, LINC02418 enhanced RASGRF1 expression by sequestering miR-494-3p, a finding substantiated by RNA pull-down assays. The tumor-suppressive effects of LINC02418 were partially reversed by RASGRF1 silencing and miR-494-3p overexpression. Clinical analyses revealed that reduced RASGRF1 expression correlated with poor histological differentiation, advanced tumor stages, and decreased overall survival in EC patients. Our findings establish LINC02418 as a tumor suppressor that regulates EC progression through modulation of the miR-494-3p/RASGRF1 axis, highlighting its potential as a therapeutic target in EC treatment.

Neurodegenerative diseases are characterized by profound differences between females and males in terms of incidence, clinical presentation, and disease progression. Furthermore, there is evidence suggesting that differences in sensitivity to medical treatments may exist between the two sexes. Although the role of sex hormones and sex chromosomes in driving differential susceptibility to these diseases is well-established, the molecular alterations underlying these differences remain poorly understood. Epigenetic mechanisms, including DNA methylation, histone tail modifications, and the activity of non-coding RNAs, are strongly implicated in the pathogenesis of neurodegenerative diseases. While it is known that epigenetic mechanisms play a crucial role in sexual differentiation and that distinct epigenetic patterns characterize females and males, sex-specific epigenetic patterns have been largely overlooked in studies aiming to identify epigenetic alterations associated with neurodegenerative diseases. This review aims to provide an overview of sex differences in epigenetic mechanisms, the role of sex-specific epigenetic processes in the central nervous system, and the main evidence of sex-specific epigenetic alterations in three neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Understanding the sex-related differences of these diseases is essential for developing personalized treatments and interventions that account for the unique epigenetic landscapes of each sex.

Super-enhancers (SEs) represent a distinct category of cis-regulatory elements notable for their robust transcriptional activation capabilities. In tumor cells, SEs intricately regulate the expression of oncogenes and pivotal cancer-associated signaling pathways, offering significant potential for cancer treatment. However, few studies have systematically discussed the crucial role of SEs in hepatocellular carcinoma (HCC), which is one of the most common liver cancers with late-stage diagnosis and limited treatment methods for advanced disease. Herein, we first summarize the identification methods and the intricate processes of formation and organization of super-enhancers. Subsequently, we delve into the roles and molecular mechanisms of SEs within the framework of HCC. Finally, we discuss the inhibitors targeting the key SE-components and their potential effects on the treatment of HCC. In conclusion, this review meticulously encapsulates the distinctive characteristics of SEs and underscores their pivotal roles in the context of hepatocellular carcinoma, presenting a novel perspective on the potential of super-enhancers as emerging therapeutic targets for HCC.

To understand the regulatory roles of miR-1972 and GZMH in hepatocellular carcinoma (HCC) and explore their potential as therapeutic biomarkers.

In vitro verification of the regulation of malignant cell behavior by differential expression of miR-1972 in HCC cells. The GSE113996 dataset was studied using weighted gene co-expression network analysis (WGCNA) and differential expressed genes respectively to identify the key prognostic gene GZMH and assess the effect of its differential expression on the prognosis of the patient. Finally, the regulation of GZMH expression by miR-1972 was verified, and the effect of their combination on HCC cell behavior was analyzed.

Inhibition of miR-1972 can reduce cell proliferation, migration, and invasion, while overexpression of miR-1972 has the opposite effect in HCC cells. According to the data, a positive prognosis for HCC was linked with higher GZMH expression. Interestingly, miR-1972 was observed to reverse-regulate the expression of GZMH. Besides, the combined regulation of GZMH and miR-1972 has been discovered to affect the cell growth, invasive capacity, and migratory potential of HCC cells, especially the cell cycle arrest in the G2 phase.

miR-1972 regulates the malignant behavior of HCC cells, especially cell proliferation, by regulating GZMH expression.

The molecular basis of adaptive evolution and cancer progression are both complex processes that share many striking similarities. The potential adaptive significance of environmentally-induced epigenetic changes is currently an area of great interest in both evolutionary and cancer biology. In the field of cancer biology intense effort has been focused on the contribution of stress-induced non-coding RNAs (ncRNAs) in the activation of epigenetic changes associated with elevated mutation rates and the acquisition of environmentally adaptive traits. Examples of this process are presented and combined with more recent findings demonstrating that stress-induced ncRNAs are transferable from somatic to germline cells leading to cross-generational inheritance of acquired adaptive traits. The fact that ncRNAs have been implicated in the transient adaptive response of various plants and animals to environmental stress is consistent with findings in cancer biology. Based on these collective observations, a general model as well as specific and testable hypotheses are proposed on how transient ncRNA-mediated adaptive responses may facilitate the transition to long-term biological adaptation in both cancer and evolution.

An appealing strategy for the treatment of several diseases is the therapeutic targeting of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). Many antisense oligonucleotides and small interfering RNAs have been tested in clinical studies over the past 10 years, and several of these have received FDA approval. However, trial results have thus far been mixed, with some studies reporting strong effects and others showing low effectiveness or side effects, including toxicity. Clinical trials for alternative entities like antimiRNAs are underway, and interest in lncRNA-based therapies is constantly growing. From this perspective, we discuss the basic overview of ncRNAs, their significant role as therapeutic biomarkers against different diseases, and the role of secondary structure in noncoding RNAs.

Life expectancy in cancer patients has been extended in recent years, thanks to major breakthroughs in therapeutic developments. However, this also unmasked an increased incidence of cardiovascular diseases in cancer survivors, which is in part attributable to cancer therapy-related cardiovascular toxicity. Non-coding RNAs (ncRNAs) have received much appreciation due to their impact on gene expression. NcRNAs, which include microRNAs, long ncRNAs and circular RNAs, are non-protein-coding transcripts that are involved in the regulation of various biological processes, hence shaping cell identity and behaviour. They have also been implicated in disease development, including cardiovascular diseases, cancer and, more recently, cancer therapy-associated cardiotoxicity. This review outlines key features of cancer therapy-associated cardiotoxicity, what is known about the roles of ncRNAs in these processes and how ncRNAs could be exploited as therapeutic targets for cardioprotection. LINKED ARTICLES: This article is part of a themed issue Non-coding RNA Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v182.2/issuetoc.

Colorectal cancer (CRC) is a common malignancy with high mortality. Despite advancements in understanding its molecular causes and improved drug therapies, patient survival rates remain low. The main reasons for the high mortality rate are cancer metastasis and the emergence of drug-resistant cancer cell populations. While genetic changes are recognized as the main driver of CRC occurrence and progression, recent studies suggest that epigenetic regulation is a crucial marker in cancer, influencing the interplay between genetics and the environment. Research has shown the significant regulatory roles of non-coding RNAs (ncRNAs) in CRC development. This review explores epigenetically regulated ncRNAs and their functions, aiming to understand key regulatory mechanisms that impact CRC development. Additionally, it discusses the potential use of these ncRNAs in CRC diagnosis, prognosis, and targeted treatments.

The epigenome coordinates spatial-temporal specific gene expression during development and in adulthood, for the maintenance of homeostasis and upon tissue repair. The upheaval of the epigenetic landscape is a key event in the onset of many pathologies including tumours, where epigenetic changes cooperate with genetic aberrations to establish the neoplastic phenotype and to drive cell plasticity during its evolution. DNA methylation, histone modifiers and readers or other chromatin components are indeed often altered in cancers, such as carcinomas that develop in epithelia. Lining the surfaces and the cavities of our body and acting as a barrier from the environment, epithelia are frequently subjected to acute or chronic tissue damages, such as mechanical injuries or inflammatory episodes. These events can activate plasticity mechanisms, with a deep impact on cells' epigenome. Despite being very effective, tissue repair mechanisms are closely associated with tumour onset. Here we review the similarities between tissue repair and carcinogenesis, with a special focus on the epigenetic mechanisms activated by cells during repair and opted by carcinoma cells in multiple epithelia. Moreover, we discuss the recent findings on inflammatory and wound memory in epithelia and describe the epigenetic modifications that characterise them. Finally, as wound memory in epithelial cells promotes carcinogenesis, we highlight how it represents an early step for the establishment of field cancerization.

Non-coding RNAs affect carcinogenic processes in diverse tissues, such as prostate. Several of these transcripts act as oncogenes driving prostate cancer. Thus, they are putative targets for treatment of this type of cancer. CRISPR/Cas9 technology has provided new tools for modulation of expression of these oncogenes in order to combat several aspects of carcinogenesis, including invasion cascades and metastasis. This review aimed to describe novel achievements in modulation of expression of non-coding RNAs using CRISPR/Cas9 technology in prostate cancer.

This research aimed to analyze alterations in microRNA expression in the diseases POF (Premature Ovarian Failure), PCOS (Polycystic Ovarian Syndrome), and ovarian cancer in order to understand the molecular changes associated with these conditions. The findings could potentially be utilized for diagnostic, therapeutic, predictive, and preventive purposes. Furthermore, the impact and role of microRNAs in each ailment, along with their functional pathways, were elucidated and examined.

In this study, the genes involved in the disease were studied, and then the miRNAs that targeted these genes were evaluated, and finally the signaling and functional pathways of each of the miRNAs were assessed. In this process, genetic databases and previous studies were carefully assessed.

miRNAs are short nucleotide sequences that belong to the category of non-coding RNAs. They play a crucial role in various physiological activities, including cell division, growth, differentiation, and cell death (necrosis and apoptosis), miRNAs are involved in various physiological processes Such alterations are common in various diseases, including cancer. miRNAs are involved in various physiological processes, such as folliculogenesis and steroidogenesis, as well as in pathological conditions such as POF, PCOS, and ovarian cancer. They have powerful regulatory effects and controlling the most activities of normal and pathological cells. While microRNAs (miRNAs) play a significant role in normal ovarian functions, there are reports of their expression changes in PCOS, ovarian cancer, and POF.

miRNAs have been found to exert significant influence on both physiological and pathological cellular processes. Understanding the dynamic patterns of miRNA alterations can provide valuable insights for researchers and therapists, enabling them to utilize these biomarkers effectively in diagnostic, therapeutic, and preventive applications.

Emerging evidence has discovered that circular RNAs play important regulators of nonsmall cell lung cancer (NSCLC), but the role and potential molecular mechanism of hsa_circ_100549 (circ_0004630) involved in NSCLC is poorly defined. In this study, circ_0004630, microRNA-1208 (miR-1208), and leucine-rich repeat kinase 2 (LRRK2) expression were detected using real-time quantitative polymerase chain reaction. Cell proliferation, colony formation, apoptosis, and invasion were assessed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine, colony formation, flow cytometry, and transwell assays. Protein levels of glucose transporter 1, Hexokinase 2, and LRRK2 were detected using western blot assay. Glucose consumption, lactate production, and adenosine triphosphate content were assessed using the corresponding kits. After predicting via bioinformatics software Circinteractome and Targetscan, the binding between miR-1208 and circ_0004630 or LRRK2 was verified by a dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assay. The xenograft tumor model analyzed the biological role circ_000460 on tumor growth in vivo. It was found that circ_0004630 and LRRK2 were increased, and miR-1208 was low expression in NSCLC tissues and cells. Functionally, the downregulation of circ_0004630 inhibited NSCLC cell proliferation, invasion, glycolysis, and accelerated apoptosis in vitro. In mechanism, circ_0004630 might work as a sponge of miR-1208 to modulate LRRK2 expression. In addition, DUXAP8 deficiency cured neuroblastoma tumor growth in vivo. In conclusion, circ_0004630 knockdown might suppress NSCLC cell proliferation, metastasis, and glycolysis partly by the miR-1208/LRRK2 axis. Our findings hinted at an important theoretical basis for further elucidating the pathogenesis of NSCLC and targeted therapy.