Search

CRISPR-Cas12a system, characterized by its precise sequence recognition and cleavage activity, has emerged as a powerful and programmable tool for molecular diagnostics. However, current CRISPR-Cas12a-based nucleic acid detection methods, particularly microRNA (miRNA) detection, necessitate additional bio-engineering strategies to exert control over Cas12a activity. Herein, we propose an engineered target-responsive hairpin DNA activator (TRHDA) to mediate forward tearing protospacer activated CRISPR-Cas12a system, which enables direct miRNA detection with high specificity and sensitivity. Target miRNA specifically binding to hairpin DNA can drive forward tearing protospacer in the stem sequence of hairpin structure, facilitating the complementarity between crRNA spacer and protospacer to activate Cas12a. Upon the hairpin DNA as input-responsive activator of Cas12a, a universal biosensing method enables the multiple miRNAs (miR-21, let-7a, miR-30a) detection and also has exceptional capability in identifying single-base mismatches and distinguishing homologous let-7/miR-30 family members. Besides, TRHDA-mediated Cas12a-powered biosensing has realized the evaluation of miR-21 expression levels in diverse cellular contexts by intracellular imaging. Considering the easy programmability of hairpin DNA in responsive region, this strategy could expand for the other target molecules detection (e.g., proteins, micromolecules, peptides, exosomes), which offers significant implications for biomarkers diagnostics utilizing the CRISPR-Cas12a system toolbox., (© 2024. The Author(s).)

Salinity adaptation is an important issue in aquaculture. Understanding the immediate-early response to salinity stress helps in comprehending this process. In vitro experiments using cell lines can explain cell-independent reactions without the involvement of hormones in vivo. In this study, salinity stress experiments were conducted using cell line derived from the gills of Gymnocypris przewalskii (GPG cell line) to isolate immediate-early response-related genes and miRNAs using transcriptomics, followed by bioinformatics analysis. The results showed that intracellular free Ca 2+ appeared to be a key factor in cell sensing and initiating downstream cell signaling in response to external salinity. Additionally, cell apoptosis was the most common feature of salinity stress, with multiple signaling pathways involved in salinity-induced cell apoptosis. Furthermore, MiRNAs played a crucial role in the rapid response to salinity stress by selectively inhibiting the expression of specific genes. Additionally, for the first time in the G. przewalskii genome, Tf2 and TY3 families of transposons were found to have responsive roles to the external salinity stress. This study contributes to a better understanding of osmotic sensing in G. przewalskii and provides theoretical assistance for improving salinity adaptation in aquaculture fish species., (© 2024. The Author(s).)

MicroRNAs are single-stranded non-coding RNAs that participate in post-transcriptional regulation of gene expression, it is involved in the regulation of apoptosis after myocardial ischemia-reperfusion injury. For example, the alteration of mitochondrial structure is facilitated by MicroRNA-1 through the regulation of apoptosis-related proteins, such as Bax and Bcl-2, thereby mitigating cardiomyocyte apoptosis. MicroRNA-21 not only modulates the expression of NF-κB to suppress inflammatory signals but also activates the PI3K/AKT pathway to mitigate ischemia-reperfusion injury. Overexpression of MicroRNA-133 attenuates reactive oxygen species (ROS) production and suppressed the oxidative stress response, thereby mitigating cellular apoptosis. MicroRNA-139 modulates the extrinsic death signal of Fas, while MicroRNA-145 regulates endoplasmic reticulum calcium overload, both of which exert regulatory effects on cardiomyocyte apoptosis. Therefore, the article categorizes the molecular mechanisms based on the three classical pathways and multiple signaling pathways of apoptosis. It summarizes the targets and pathways of MicroRNA therapy for ischemia-reperfusion injury and analyzes future research directions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

MicroRNA (miRNA) is a class of non-coding endogenous small-molecule, single-stranded RNAs, and it is involved in post-transcriptional gene expression regulation in plants and plays an important role in plant growth and development. Among them, miRNA156 regulates members of target SPL gene family and thus participates in plant growth and development, hormonal response and adversity stress. However, it has not been reported in ginseng. In this study, based on the previous analysis of the SPL gene family, the age-related and stably expressed SPL gene PgSPL24-09 was obtained in roots. The binding site of miRNA156 to this gene was analyzed using target gene prediction tools, and the interactions between miRNA156 and PgSPL24-09 gene were verified by dual luciferase reporter gene assay and RT-qPCR. At the same time, miRNA156 silencing vector and overexpression vector were constructed and transformed into ginseng adventitious roots and Arabidopsis thaliana to analyze the molecular mechanism of miRNA156-SPL module in regulating the growth of ginseng adventitious roots. This study provides a theoretical basis for the in-depth study of the molecular role of miRNAs in ginseng growth, and also lays the foundation for the study of the role of miRNA156-SPL module in regulating the growth and development of ginseng., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Mingzhu Zhao, Kangyu Wang reports financial support was provided by Department of Science and Technology of Jilin Province (20240402046 GH). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Replacement of beta cells through transplantation is a potential therapeutic approach for individuals with pancreas removal or poorly controllable type 1 diabetes. However, stress and death of beta cells pose significant challenges. Circulating miRNA has emerged as potential biomarkers reflecting early beta cell stress and death, allowing for timely intervention. The aim of this study was to identify miRNAs as potential biomarkers for beta cell health. Literature review combined with small RNA sequencing was employed to select islet-enriched miRNA. The release of those miRNA was assessed by RT-qPCR in vivo , using a streptozotocin induced diabetes mouse model and in vitro , through mouse and human islets exposed to varying degrees of hypoxic and cytokine stressors. Utilizing the streptozotocin induced model, we identified 18 miRNAs out of 39 candidate islet-enriched miRNA to be released upon islet stress in vivo . In vitro analysis of culture supernatants from cytokine and/or hypoxia stressed islets identified the release of 45 miRNAs from mouse and 8 miRNAs from human islets. Investigation into the biological pathways targeted by the cytokine- and/or hypoxia-induced miRNA suggested the involvement of MAPK and PI3K-Akt signaling pathways in both mouse and human islets. We have identified miRNAs associated with beta cell health and stress. The findings allowed us to propose a panel of 47 islet-related human miRNA that is potentially valuable for application in clinical contexts of beta cell transplantation and presymptomatic early-stage type 1 diabetes.

Eggshell color plays important biological roles and attracts the attention of both egg retailers and researchers. However, whether non-coding RNAs are involved in pigment deposition among different eggshell colors remains unknown. In this study, RNA sequencing was used to analyse the uterine gland transcriptome (CircRNA and miRNA) of Changshun chicken blue-shell hens producing four different eggshell color eggs including dark blue PK(DB) and light blue (LB), dark brown and greenish (between blue and pink, DP) and pink (p). We found that miR-192-x , targeting SLC16a7 , was expressed in DB, DP, and LB groups compared with the PK group, which indicates that miR-192-x may play a role in the blue eggshell color. KEGG and GO analyses showed that the "metabolic pathways" with targeted genes such BLVRA and HMOX1 were detected in dark and light blue color eggshell chickens, which confirms the different ratios of biliverdin and HO-1 involved in the deposition of blue color. As annotated by connectivity analysis, RASGRF1 and RASGRF2 , belonging to the RASGRF family, are involved in the Ras signaling pathway, which plays an important role in cell growth, differentiation, metastasis and apoptosis. Our findings enrich the database of circRNA, miRNAs and genes for chicken uterine tissue, which will be useful in accelerating molecular selection for blue eggshell color layers.

Recent studies on co-transformation of the growth regulator, TaGRF4-GIF1 chimera (Growth Regulating Factor 4-GRF Interacting Factor 1), in cultivated wheat varieties (Triticum aestivum), showed improved regeneration efficiency, marking a significant breakthrough. Here, a simple and reproducible protocol using the GRF4-GIF1 chimera was established and tested in the medicinal orchid Dendrobium catenatum, a monocot orchid species. TaGRF4-GIF1 from T. aestivum and DcGRF4-GIF1 from D. catenatum were reconstructed, with the chimeras significantly enhancing the regeneration efficiency of D. catenatum through in planta transformation. Further, mutating the microRNA396 (miR396) target sites in TaGRF4 and DcGRF4 improved regeneration efficiency. The target mimicry version of miR396 (MIM396) not only boosted shoot regeneration but also enhanced plant growth. Our methods revealed a powerful tool for the enhanced regeneration and genetic transformation of D. catenatum., (© 2024. The Author(s).)

As sessile organisms, plants experience variable environments and encounter diverse stresses during their growth and development. Adventitious rooting, orchestrated by multiple coordinated signaling pathways, represents an adaptive strategy evolved by plants to adapt to cope with changing environmental conditions. This study uncovered the role of the miR159a-PeMYB33 module in the formation of adventitious roots (ARs) synergistically with abscisic acid (ABA) signaling in poplar. Overexpression of miR159a increased the number of ARs and plant height while reducing sensitivity to ABA in transgenic plants. In contrast, inhibition of miR159a (using Short Tandem Target Mimic) or overexpression of PeMYB33 decreased the number of ARs in transgenic plants. Additionally, miR159a targets and cleaves transcripts of PeMYB33 using degradome analysis, which was further confirmed by a transient expression experiment of poplar protoplast. We show the miR159a-PeMYB33 module controls ARs development in poplar through ABA signaling. In particular, we demonstrated that miR159a promotes the expression of genes in the ABA signaling pathway. The findings from this study shed light on the intricate regulatory mechanisms governing the development of ARs in poplar plants. The miR159a-PeMYB33 module, in conjunction with ABA signaling, plays a crucial role in modulating AR formation and subsequent plant growth., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

CircRNAs are abnormally expressed in various cancers and play an important role in the occurrence and development of cancers. However, their biological functions and the underlying molecular mechanisms in pancreatic cancer (PC) metastasis are incompletely understood. Differentially expressed circRNAs were identified by second-generation transcriptome sequencing in three pairs of PC tissues and adjacent tissues. The expression and prognostic significance of hsa_circ_0007919 were evaluated by qRT-PCR and Kaplan-Meier survival curves. Gain- and loss-of-function assays were conducted to detect the role of hsa_circ_0007919 in PC metastasis in vitro. A lung metastasis model and IHC experiments were conducted to confirm the effects of hsa_circ_0007919 on tumor metastasis in vivo. Mechanistically, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to explore the interplay among hsa_circ_0007919, Sp1, and the THBS1 promoter. hsa_circ_0007919 was significantly upregulated in PC tissues and cells and was correlated with lymph node metastasis, TNM stage, and poor prognosis. Knockdown of hsa_circ_0007919 significantly suppressed the migration and invasion of PC cells in vitro and inhibited tumor metastasis in vivo. However, overexpression of hsa_circ_0007919 exerted the opposite effects. Mechanistically, hsa_circ_0007919 could recruit the transcription factor Sp1 to inhibit THBS1 transcription, thereby facilitating PC metastasis. hsa_circ_0007919 can promote the metastasis of PC by inhibiting THBS1 expression. hsa_circ_0007919 may be a potential therapeutic target in PC., (© 2024 Federation of American Societies for Experimental Biology.)

Alzheimer's disease (AD) and post-stroke cognitive impairment (PSCI) are the leading causes of progressive dementia related to neurodegenerative and cerebrovascular injuries in elderly populations. Despite decades of research, patients with these conditions still lack minimally invasive, low-cost, and effective diagnostic and treatment methods. MicroRNAs (miRNAs) play a vital role in AD and PSCI pathology. As they are easily obtained from patients, miRNAs are promising candidates for the diagnosis and treatment of these two disorders. In this study, we performed complete sequencing analysis of miRNAs from 24 participants, split evenly into the PSCI, post-stroke non-cognitive impairment (PSNCI), AD, and normal control (NC) groups. To screen for differentially expressed miRNAs (DE-miRNAs) in patients, we predicted their target genes using bioinformatics analysis. Our analyses identified miRNAs that can distinguish between the investigated disorders; several of them were novel and never previously reported. Their target genes play key roles in multiple signaling pathways that have potential to be modified as a clinical treatment. In conclusion, our study demonstrates the potential of miRNAs and their key target genes in disease management. Further in-depth investigations with larger sample sizes will contribute to the development of precise treatments for AD and PSCI., (© 2024. The Author(s).)

MicroRNA482/2118 (miR482/2118) is a 22-nt miRNA superfamily, with conserved functions in disease resistance and plant development. It usually instigates the production of phased small interfering RNAs (phasiRNAs) from its targets to expand or reinforce its silencing effect. Using a new high-quality reference genome sequence and comprehensive small RNA profiling, we characterized a newly evolved regulatory pathway of miR482/2118 in litchi. In this pathway, miR482/2118 cleaved a novel noncoding trans-acting gene (LcTASL1) and triggered phasiRNAs to regulate the expression of gibberellin (GA) receptor gene GIBBERELLIN INSENSITIVE DWARF1 (GID1) in trans; another trans-acting gene LcTASL2, targeted by LcTASL1-derived phasiRNAs, produced phasiRNAs as well to target LcGID1 to reinforce the silencing effect of LcTASL1. We found this miR482/2118-TASL-GID1 pathway was likely involved in fruit development, especially the seed development in litchi. In vivo construction of the miR482a-TASL-GID1 pathway in Arabidopsis could lead to defects in flower and silique development, analogous to the phenotype of gid1 mutants. Finally, we found that a GA-responsive transcription factor, LcGAMYB33, could regulate LcMIR482/2118 as a feedback mechanism of the sRNA-silencing pathway. Our results deciphered a lineage-specifically evolved regulatory module of miR482/2118, demonstrating the high dynamics of miR482/2118 function in plants., (© 2023 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.)

In the past several years, with the in-depth development of RNA-related research, exploring the application of transcriptome and corresponding RNA biomarkers has become one of the research hotspots in the field of forensic science. High-quality RNA is essential for successful downstream workflows, especially in the steps of screening biomarkers by microarray or RNA sequencing (RNA-seq). Thus, accurately evaluating the quality of RNA samples is a critical step in obtaining meaningful expression data. The RNA integrity number (RIN) generated from the Agilent Bioanalyzer system has been widely used for RNA quality control in the past two decades. Recently, Thermo Fisher Scientific launched a ratiometric fluorescence-based method to quickly check whether an RNA sample has degraded, and the results are presented as RNA integrity and quality number (RNA IQ). Both quality score systems determine RNA quality using a numerical system based on a scale of 1-10, with 1 denoting significantly degraded specimens and 10 representing high-quality, intact RNA samples. In this preliminary study, we evaluated the consistency, reproducibility and linearity of two quality scores in RNA quality determination by analyzing heat- and RNase- artificially degraded samples. Meanwhile, the expression levels of three microRNAs (hsa-let-7 g-5p, hsa-miR-93-5p and hsa-miR-191-5p) in intact and severely degraded RNA samples were estimated by TaqMan-qPCR and droplet digital PCR. Overall, both quality scores showed good repeatability and reproducibility in their respective tests. In the samples subjected to thermal degradation, RIN showed a trend corresponding to heating time, while RNA IQ value showed almost no change on the time gradient. However, in RNase A mediated degradation, RNA IQ value observed better linearity. Furthermore, the expression levels of three microRNAs in the severely degraded samples did not show significant changes compared to the intact RNA samples. RNA degradation is a very complex and highly variable process, which is difficult to comprehensively evaluate through any one index and cannot directly compare these two parameters. Nevertheless, combined with previous research results and the expression levels of three microRNAs in this study, analyzing RNA biomarkers with stable regions or small sizes in challenged samples may be a conservative and reliable approach., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cytochrome P450 monooxygenases (P450s) are recognized as a major contributor to metabolic resistance in insects to most insecticides, through gene overexpressions and protein mutations. MicroRNA (miRNA), an important post-transcriptional regulator, has been reported to promote insecticide resistance by mediating the expression of detoxification enzyme genes., Results: In the present study, we reported that a novel microRNA PC-5p-3991_515 was involved in the post-transcriptional regulation of CYP417A2 and mediated the triflumezopyrim susceptibility in the small brown planthopper (SBPH), Laodelphax striatellus (Fallén). The tissue expression profiles showed that CYP417A2 was highly expressed in fat body. CYP417A2 was significantly up-regulated at 12, 36, 60, 84 and 108 h after the triflumezopyrim treatment. RNA interference (RNAi) against CYP417A2 significantly increased triflumezopyrim susceptibility in SBPH. According to the prediction by miRanda and TargetScan software, three miRNAs were indicated to bind to CYP417A2. However, when oversupply of agomir, only two miRNAs, PC-3p-625_4405 and PC-5p-3991_515, significantly increased the susceptibility to triflumezopyrim and decreased CYP417A2 levels. Furthermore, PC-5p-3991_515 was confirmed to be involved in the post-transcriptional regulation of CYP417A2 by dual luciferase reporter assay. Meanwhile, PC-5p-3991_515 was co-localized with CYP417A2 in the midgut in situ hybridization., Conclusion: Our findings revealed that the novel microRNA, PC-5p-3991_515, post-transcriptionally regulated CYP417A2 expression, which then mediated the triflumezopyrim susceptibility in SBPH. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: miR-182 promoter hypermethylation frequently occurs in various tumors, including acute myeloid leukemia, and leads to low expression of miR-182. However, whether adult acute lymphocyte leukemia (ALL) cells have high miR-182 promoter methylation has not been determined., Methods: To assess the methylation status of the miR-182 promoter, methylation and unmethylation-specific PCR analysis, bisulfite-sequencing analysis, and MethylTarget™ assays were performed to measure the frequency of methylation at the miR-182 promoter. Bone marrow cells were isolated from miR-182 knockout (182KO) and 182 wild type (182WT) mice to construct BCR-ABL (P190) and Notch-induced murine B-ALL and T-ALL models, respectively. Primary ALL samples were performed to investigate synergistic effects of the hypomethylation agents (HMAs) and the BCL2 inhibitor venetoclax (Ven) in vitro., Results: miR-182 (miR-182-5P) expression was substantially lower in ALL blasts than in normal controls (NCs) because of DNA hypermethylation at the miR-182 promoter in ALL blasts but not in normal controls (NCs). Knockout of miR-182 (182KO) markedly accelerated ALL development, facilitated the infiltration, and shortened the OS in a BCR-ABL (P190)-induced murine B-ALL model. Furthermore, the 182KO ALL cell population was enriched with more leukemia-initiating cells (CD43 + B220 + cells, LICs) and presented higher leukemogenic activity than the 182WT ALL population. Furthermore, depletion of miR-182 reduced the OS in a Notch-induced murine T-ALL model, suggesting that miR-182 knockout accelerates ALL development. Mechanistically, overexpression of miR-182 inhibited proliferation and induced apoptosis by directly targeting PBX3 and BCL2, two well-known oncogenes, that are key targets of miR-182. Most importantly, DAC in combination with Ven had synergistic effects on ALL cells with miR-182 promoter hypermethylation, but not on ALL cells with miR-182 promoter hypomethylation., Conclusions: Collectively, we identified miR-182 as a tumor suppressor gene in ALL cells and low expression of miR-182 because of hypermethylation facilitates the malignant phenotype of ALL cells. DAC + Ven cotreatment might has been applied in the clinical try for ALL patients with miR-182 promoter hypermethylation. Furthermore, the methylation frequency at the miR-182 promoter should be a potential biomarker for DAC + Ven treatment in ALL patients., (© 2024. The Author(s).)

Background: There is increasing evidence that circular RNAs (circRNAs) are involved in the processes of preeclampsia (PE). Circ_0030042 was found to be abnormally expressed in PE patients. However, the role and molecular mechanism of circ_0030042 in PE progression remains unclear., Methods: Quantitative real-time PCR was used for determining the expression of circ_0030042, microRNA (miR)- 942-5p and lipopolysaccharide induced TNF-α factor (LITAF). Trophoblast cell functions were determined using cell counting kit 8 assay, EdU assay, flow cytometry and transwell assay. The protein levels of epithelial-mesenchymal transition (EMT)-related markers and LITAF were examined using western blot analysis. Dual-luciferase reporter assay and RNA pull-down assay were used to verify RNA interaction., Results: Circ_0030042 had an elevated expression in PE patients, and its overexpression inhibited trophoblast cell growth, invasion, and EMT process. Circ_0030042 served as miR-942-5p sponge, and miR-942-5p inhibitor also reversed the regulation of circ_0030042 on trophoblast cell growth, invasion and EMT process. LITAF was targeted by miR-942-5p, and its knockdown abolished the inhibition effect of miR-942-5p on trophoblast cell growth, invasion, and EMT process. Also, circ_0030042 regulated LITAF expression via sponging miR-942-5p., Conclusion: Circ_0030042 regulated trophoblast cell growth, invasion, and EMT process via the miR-942-5p/LITAF axis, providing a novel insight for PE treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Drought stress has been a key environmental factor affecting plant growth and development. The plant genome is capable of producing long noncoding RNAs (lncRNAs). To better understand white mulberry (Morus alba L.) drought response mechanism, we conducted a comparative transcriptome study comparing two treatments: drought-stressed (EG) and well-watered (CK) plants. A total of 674 differentially expressed lncRNAs (DElncRNAs) were identified. In addition, 782 differentially expressed messenger RNAs (DEmRNAs) were identified. We conducted Gene Ontology (GO) and KEGG enrichment analyses focusing on the differential lncRNAs cis-target genes. The target genes of the DElncRNAs were most significantly involved in the biosynthesis of secondary metabolites. Gene regulatory networks of the target genes involving DElncRNAs-mRNAs-DEmRNAs and DElncRNA-miRNA-DEmRNA were constructed. In the DElncRNAs-DEmRNAs network, 30 DEmRNAs involved in the biosynthesis of secondary metabolites are collocated with 46 DElncRNAs. The interaction between DElncRNAs and candidate genes was identified using LncTar. In summary, quantitative real-time polymerase chain reaction (qRT-PCR) validated nine candidate genes and seven target lncRNAs including those identified by LncTar. We predicted that the DElncRNAs-DEmRNAs might recruit microRNAs (miRNAs) to interact with gene regulatory networks under the drought stress response in mulberry. The findings will contribute to our understanding of the regulatory functions of lncRNAs under drought stress and will shed new light on the mulberry-drought stress interactions., (© 2022 The Authors. The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Background: Nitric oxide (NO) is the most important vasodilator secreted by vascular endothelial cells, and its abnormal synthesis is involved in the development of cardiovascular disease. The prenatal period is a critical time for development and largely determines lifelong vascular health in offspring. Given the high incidence and severity of gestational hypoxia in mid-late pregnancy, it is urgent to further explore whether it affects the long-term synthesis of NO in offspring vascular endothelial cells., Methods and Results: Pregnant Sprague-Dawley rats were housed in a normoxic or hypoxic (10.5% O 2 ) chamber from gestation days 10 to 20. The thoracic aortas of fetal and adult male offspring were isolated for experiments. Gestational hypoxia significantly reduces the NO-dependent vasodilation mediated by acetylcholine in both the fetal and adult offspring thoracic aorta rings. Meanwhile, acetylcholine-induced NO synthesis is impaired in vascular endothelial cells from hypoxic offspring thoracic aortas. We demonstrate that gestational hypoxic offspring exhibit a reduced endothelial NO synthesis capacity, primarily due to increased expression of NADPH oxidase 2 and enhanced reactive oxygen species. Additionally, gestational hypoxic offspring show elevated levels of miR-155-5p in vascular endothelial cells, which is associated with increased expression of NADPH oxidase 2 and reactive oxygen species generation, as well as impaired NO synthesis., Conclusions: The present study is the first to demonstrate that gestational hypoxia impairs endothelial NO synthesis via the miR-155-5p/NADPH oxidase 2/reactive oxygen species axis in offspring vessels. These novel findings indicate that the detrimental effects of gestational hypoxia on fetal vascular function can persist into adulthood, providing new insights into the development of vascular diseases.

Background: The right ventricle (RV) is at risk in patients with complex congenital heart disease involving right-sided obstructive lesions. We have shown that capillary rarefaction occurs early in the pressure-loaded RV. Here we test the hypothesis that microRNA (miR)-34a, which is induced in RV hypertrophy and RV failure (RVF), blocks the hypoxia-inducible factor-1α-vascular endothelial growth factor (VEGF) axis, leading to the attenuated angiogenic response and increased susceptibility to RV failure., Methods and Results: Mice underwent pulmonary artery banding to induce RV hypertrophy and RVF. Capillary rarefaction occurred immediately. Although hypoxia-inducible factor-1α expression increased (0.12±0.01 versus 0.22±0.03, P =0.05), VEGF expression decreased (0.61±0.03 versus 0.22±0.05, P =0.01). miR-34a expression was most upregulated in fibroblasts (4-fold), but also in cardiomyocytes and endothelial cells (2-fold). Overexpression of miR-34a in endothelial cells increased cell senescence (10±3% versus 22±2%, P <0.05) by suppressing sirtulin 1 expression, and decreased tube formation by 50% via suppression of hypoxia-inducible factor-1α, VEGF A, VEGF B, and VEGF receptor 2. miR-34a was induced by stretch, transforming growth factor-β1, adrenergic stimulation, and hypoxia in cardiac fibroblasts and cardiomyocytes. In mice with RVF, locked nucleic acid-antimiR-34a improved RV shortening fraction and survival half-time and restored capillarity and VEGF expression. In children with congenital heart disease-related RVF, RV capillarity was decreased and miR-34a increased 5-fold., Conclusions: In summary, miR-34a from fibroblasts, cardiomyocytes, and endothelial cells mediates capillary rarefaction by suppressing the hypoxia-inducible factor-1α-VEGF axis in RV hypertrophy/RVF, raising the potential for anti-miR-34a therapeutics in patients with at-risk RVs.

There is a cross-link between the placenta and cancer development, as the placenta is grown as a highly invasive tumour-like organ. However, placental development is strictly controlled. Although the underlying mechanism of this control is largely unknown, it is now well-recognised that extracellular vesicles (EVs) released from the placenta play an important role in controlling placenta proliferation and invasion, as placental EVs have shown their effect on regulating maternal adaptation. Better understanding the tumour-like mechanism of the placenta could help to develop a therapeutic potential in cancers. In this study, by RNA sequencing of placental EVs, 20 highly expressed microRNAs (miRNAs) in placental EVs were selected and analysed for their functions on ovarian and endometrial cancer. There were up to seven enriched miRNAs, including miRNA-199a-3p, miRNA-143-3p, and miRNA-519a-5p in placental EVs showing effects on the inhibition of ovarian and endometrial cancer cell proliferation and migration, and promotion of cancer cell death, reported in the literature. Most of these miRNAs have been reported to be downregulated in ovarian and endometrial cancer. Transfection of ovarian and endometrial cancer cells with mimics of miRNA-199a-3p, miRNA-143-3p, and miRNA-519a-5p significantly reduced the cell viability. Our findings could provide strategies for using these naturally occurring miRNAs to develop a novel method to treat ovarian and endometrial cancer in the future., (© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.)

Objectives: Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear., Methods: Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1., Results: Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells., Conclusions: In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. To develop a vascular adventitial drug delivery system to treat intimal hyperplasia post vascular injuries, we loaded miR-145-5p-agomir (miR-145) into an injectable and in-situ self-assembling RAD peptide hydrogel. In vitro data showed that the miR-145 could be well incorporated into the RAD peptide hydrogels and released in a slow and controlled manner. The released miR-145 could transfect SMCs successfully, and the transfected SMCs exhibited a reduced migration capacity and higher expressions of SMC contractile biomarkers as compared to the non-transfected SMCs. In vivo data showed that the retention of the miR-145 was greatly elongated by the RAD peptide hydrogels. In addition, the application of the miR-145-loaded RAD peptide hydrogels surrounding injured arteries decreased the proliferative SMCs, promoted the regeneration of endothelium, reduced the macrophage infiltration, inhibited the neointimal formation and prevented adverse ECM remodeling via downregulation of KLF4 expression. The RAD peptide hydrogels loaded with miR-145 can successfully inhibit intimal hyperplasia after vascular injuries and thus hold great potential as an innovative extravascular drug delivery approach to treat vascular diseases. STATEMENT OF SIGNIFICANCE: Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. Our work here demonstrates that the RAD peptide hydrogels loaded with miR-145-5p-agomir (miR-145) can successfully reverse intimal hyperplasia after vascular injuries and thus hold great potential as an innovative vascular adventitial drug delivery approach to treat vascular diseases. Our work proposes a possible paradigm shift from endovascular drug delivery to extravascular drug delivery for vascular disorder treatment., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Circular RNAs (circRNAs) are critical regulators of lung adenocarcinoma (LA) progression. Although a molecular marker targeting hsa&#95;circ&#95;0000018 has been developed and used for diagnosing colon cancer, the role of this circRNA in LA progression has not been explored till now., Objectives: This study aimed to elucidate the role and regulatory mechanisms of hsa&#95;circ&#95;0000018 in LA progression., Methods: LA tissues and corresponding adjacent non-tumor tissues were collected from 36 patients to confirm the levels of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). We also cultured two LA cell lines (A549, PC-9), and the human normal lung epithelial cell line BEAS-2B. Cell function experiments were conducted to assess malignancy in LA cells, including proliferation, migration, and invasion, following forced hsa&#95;circ&#95;0000018 expression. The correlation between hsa&#95;circ&#95;0000018, let-7f-5p, and family with sequence similarity 96 member A (FAM96A) was confirmed by using starBase (miRNA-circRNA interaction database), luciferase assay, and western blotting., Results: Expression of hsa&#95;circ&#95;0000018 and FAM96A was reduced, whereas that of let-7f-5p was upregulated in LA. Cell function assays revealed that upregulation of hsa&#95;circ&#95;0000018 had a suppressive effect on the proliferation, migration, and invasion of LA cells. Additionally, hsa&#95;circ&#95;0000018 sponge binds let-7f-5p, resulting in upregulation of FAM96A expression., Conclusion: Our data reveal hsa&#95;circ&#95;0000018 as a tumor suppressor in LA that targets the let-7f-5p/FAM96A axis. Our findings enrich the known regulatory network of circRNAs in LA.

Introduction: Olfactory ensheathing cells (OECs) are important transplantable cells for the treatment of spinal cord injury. However, information on the mechanism of OEC-derived extracellular vesicles (EVs) in nerve repair is scarce., Methods: We cultured OECs and extracted the OEC-derived EVs, which were identified using a transmission electron microscope, nanoparticle flow cytometry, and western blotting. High throughput RNA sequencing of OECs and OEC-EVs was performed, and the differentially expressed microRNAs (miRNAs) (DERs) were analyzed by bioinformatics. The target genes of DERs were identified using miRWalk, miRDB, miRTarBase, and TargetScan databases. Gene ontology and KEGG mapper tools were used to analyze the predicted target genes. Subsequently, the STRING database and Cytoscape software platform were used to analyze and construct miRNA target genes' protein-protein interaction (PPI) network., Results: Overall, 206 miRNAs (105 upregulated and 101 downregulated) were differentially expressed in OEC-EVs (p < 0.05;|log2 (fold change)|>2). Six DERs (rno-miR-7a-5p, rno-miR-143-3p, rno-miR-182, rno-miR-214-3p, rno-miR-434-5p, rno-miR-543-3p) were significantly up-regulated , and a total of 974 miRNAs target genes were obtained. The target genes were mainly involved in biological processes such as regulation of cell size, positive regulation of cellular catabolic process and small GTPase-mediated signal transduction; positive regulation of genes involved in cellular components such as growth cone, site of polarized growth, and distal axon; and molecular functions such as small GTPase binding and Ras GTPase binding. In pathway analysis, target genes regulated by six DERs were mainly enriched in axon guidance, endocytosis, and Ras and cGMP-dependent protein kinase G signaling pathways. Finally, 19 hub genes were identified via the PPI network., Conclusion: Our study provides a theoretical basis for treating nerve repair by OEC-derived EVs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Importance: Kidney injury during acute urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) is an important public health problem. However, how kidney injury develops during UPEC infection is still unclear. Although antibiotic therapy is currently an effective treatment for UTI, it cannot avoid kidney injury. MicroRNAs have gained extensive attention as essential molecules capable of regulating the autoimmune response. Among these, microRNA-146b (miR-146b) is involved in regulating inflammatory responses. In the present study, we demonstrated that miR-146b played an essential role in the development of kidney injury during UTIs caused by UPEC. The results showed that miR-146b may suppress M1 macrophage polarization and alleviate acute kidney injury. Furthermore, the miR-146b activator, agomir, in order to upregulate miR-146b, was effective in treating kidney damage by inhibiting the activation of M1 macrophages. In conclusion, our findings elucidated the mechanisms by which miR-146b alleviated kidney injury induced by UTIs, shed new light on the relationship between microRNA and bacterial infection, and provided a novel therapeutic target for treating this common bacterial infection., Competing Interests: The authors declare no conflict of interest.

Osteogenic differentiation, proliferation, and/or apoptosis of bone marrow mesenchymal stem cells (BMSCs) are involved in the progression of postmenopausal osteoporosis (PMO). However, circular RNA (circRNA)-mediated changes in the cellular function of BMSCs in PMO are still unclear. This study revealed the excellent ability of circ-Plod2 to promote osteogenic differentiation of BMSCs and its molecular mechanisms. In this study, ovariectomized (OVX) rats and control (Sham) rats were used to simulate PMO. Initially, we found that the expression of circ-Plod2 in OVX BMSCs is down-regulated and the expression of the Mpo gene is up-regulated by sequencing and verification. Further, we confirmed that circ-Plod2 is located in the cytoplasm and belongs to exon-type circRNA. Interestingly, circ-Plod2 promotes Mpo-dependent osteogenic differentiation of BMSCs without affecting proliferation, apoptosis, adipogenic differentiation, or chondrogenic differentiation of BMSCs. Mechanistically, we demonstrated that circ-Plod2 specifically binds IGF2BP2 to form an RNA-protein complex that destabilizes Mpo mRNA. Overexpression of circ-Plod2 in the bone marrow cavity effectively alleviated osteoporosis in OVX rats and inhibited the expression of MPO in BMSCs. Together, this study reveals that circ-Plod2 destabilizes Mpo mRNA by binding to IGF2BP2 to promote osteogenic differentiation of BMSCs to alleviate osteoporosis. The findings of this study may provide biomarkers for the diagnosis of PMO, and may also provide potential strategies for the clinical treatment of PMO., Competing Interests: Declaration of competing interest The authors have declared that no competing interest exists., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer and chemoresistance. DNA damage repair contributes to the proliferation of cancer cells and resistance to chemotherapy-induced apoptosis. However, the role of circRNAs in the regulation of DNA damage repair needs clarification., Methods: RNA sequencing analysis was applied to identify the differentially expressed circRNAs. qRT-PCR was conducted to confirm the expression of hsa&#95;circ&#95;0007919, and CCK-8, FCM, single-cell gel electrophoresis and IF assays were used to analyze the proliferation, apoptosis and gemcitabine (GEM) resistance of pancreatic ductal adenocarcinoma (PDAC) cells. Xenograft model and IHC experiments were conducted to confirm the effects of hsa&#95;circ&#95;0007919 on tumor growth and DNA damage in vivo. RNA sequencing and GSEA were applied to confirm the downstream genes and pathways of hsa&#95;circ&#95;0007919. FISH and nuclear-cytoplasmic RNA fractionation experiments were conducted to identify the cellular localization of hsa&#95;circ&#95;0007919. ChIRP, RIP, Co-IP, ChIP, MS-PCR and luciferase reporter assays were conducted to confirm the interaction among hsa&#95;circ&#95;0007919, FOXA1, TET1 and the LIG1 promoter., Results: We identified a highly expressed circRNA, hsa&#95;circ&#95;0007919, in GEM-resistant PDAC tissues and cells. High expression of hsa&#95;circ&#95;0007919 correlates with poor overall survival (OS) and disease-free survival (DFS) of PDAC patients. Hsa&#95;circ&#95;0007919 inhibits the DNA damage, accumulation of DNA breaks and apoptosis induced by GEM in a LIG1-dependent manner to maintain cell survival. Mechanistically, hsa&#95;circ&#95;0007919 recruits FOXA1 and TET1 to decrease the methylation of the LIG1 promoter and increase its transcription, further promoting base excision repair, mismatch repair and nucleotide excision repair. At last, we found that GEM enhanced the binding of QKI to the introns of hsa&#95;circ&#95;0007919 pre-mRNA and the splicing and circularization of this pre-mRNA to generate hsa&#95;circ&#95;0007919., Conclusions: Hsa&#95;circ&#95;0007919 promotes GEM resistance by enhancing DNA damage repair in a LIG1-dependent manner to maintain cell survival. Targeting hsa&#95;circ&#95;0007919 and DNA damage repair pathways could be a therapeutic strategy for PDAC., (© 2023. The Author(s).)

Objective: High-throughput sequencing was used to screen expressing differences of miRNA, lncRNA, and mRNA in CD19+ B peripheral blood samples of newly diagnosed immune thrombocytopenia (ITP) patients and healthy controls. The study aimed to explore the regulatory role of ceRNA network in the pathogenesis of dysfunctional CD19 + B lymphocytes of ITP patients., Methods: CD19+ B lymphocytes were isolated from peripheral blood samples of ITP patients and their healthy counterparts. High-throughput sequencing was used to screen for the expression of miRNA, lncRNA, and mRNA of ITP patients and healthy controls, which were analysed by the ceRNA network. Moreover, qPCR was used to verify the differential expression of miRNA, lncRNA, and mRNA in ITP patients and healthy controls. The correlation between differentially expressed miRNA, lncRNA, mRNA, and B lymphocyte subsets was also analysed., Results: The CD19+ B lymphocytes of 4 newly diagnosed ITP patients and 4 healthy controls were sequenced and analysed. There were 65 differentially expressed lncRNA and 149 mRNA forming a ceRNA network showed that 12 lncRNA and 136 differentially expressed mRNA were closely associated. Similarly, miR-144-3p, miR-374c-3p, and miR-451a were highly expressed in ITP patients, as confirmed by qPCR, which was consistent with the high-throughput sequence results. LOC102724852 and CCL20 were highly expressed in ITP patients, while LOC105378901, LOC112268311, ALAS2, and TBC1D3F were not as compared to healthy controls, which was consistent with the high-throughput sequence results. In addition, the expression of miR-374c-3p, LOC112268311, LOC105378901, and CXCL3 were correlated with the percentage of B lymphocyte subsets., Conclusions: The ceRNA network of miRNA, lncRNA, and mRNA in peripheral CD19 + B lymphocytes plays an essential role in the pathogenesis of ITP.

Cervical cancer is one of the most common gynecological cancers with high metastasis, poor prognosis and conventional chemotherapy. The long non-coding RNA (lncRNA) ABHD11 antisense RNA 1 (ABHD11-AS1) plays a vital role in tumorigenesis and is involved in cell proliferation, differentiation, and apoptosis. Especially for cervical cancer, the functions and mechanisms of ABHD11-AS1 are still undetermined. In this study, we explored the role and underlying mechanism of ABHD11-AS1 in cervical cancer. We found that ABHD11-AS1 is highly expressed in cervical cancer tissue. The roles of ABHD11-AS1 and EGFR have investigated the loss of function analysis and cell movability in SiHa and Hela cells. Knockdown of ABHD11-AS1 and EGFR significantly inhibited the proliferation, migration, and invasion and promoted apoptosis of SiHa and Hela cells by up-regulating p21 and Bax and down-regulating cyclin D1, Bcl2, MMP9, and Vimentin. ABHD11-AS1 knockdown could decrease the expression of EGFR. In addition, ABHD11-AS1 could regulate the EGFR signaling pathway, including p-EGFR, p-AKT, and p-ERK. Spearman's correlation analysis and cell experiments demonstrated that ABHD11 was highly expressed in tumor tissue and partially offset the effect of shABHD11-AS1 on the proliferation, migration, and invasion of SiHa and Hela cells. Then, RNA pulldown was used to ascertain the mechanisms of ABHD11-AS1 and FUS. ABHD11-AS1 inhibited ABHD11 mRNA degradation by bounding to FUS. A subcutaneous xenograft of SiHa cells was established to investigate the effect of ABHD11-AS1 in tumor tissue. Knockdown of ABDH11-AS1 inhibited tumor growth and decreased the tumor volume. ABHD11-AS1 knockdown inhibited the expression of Ki67 and Vimentin and up-regulated the expression of Tunel. Our data indicated that ABHD11-AS1 promoted cervical cancer progression by activating EGFR signaling, preventing FUS-mediated degradation of ABHD11 mRNA. Our findings provide novel insights into the potential role of lncRNA in cervical cancer therapy.

Activated microglia play dual roles in ischemic stroke (IS) according to its polarization states. Herein, we investigated the function of circPTP4A2 in regulating microglia polarization in IS. IS models were established by MACO/R and OGD/R treatment. TTC staining was employed to detect cerebral infarct size. Cell vitality was measured using CCK-8 assay. CD16 and CD206 levels were examined using flow cytometry. The interactions between circPTP4A2, miR-20b-5p, and YTHDF1 were analyzed by dual-luciferase reporter gene, RIP, or RNA pull-down assays. circPTP4A2 was upregulated in IS patients. circPTP4A2 knockdown alleviated MCAO/R-induced cerebral injury in mice. circPTP4A2 knockdown promoted microglia M2 polarization after OGD/R. circPTP4A2 promoted YTHDF1 expression by sponging miR-20b-5p. The promoting effect of circPTP4A2 knockdown on microglia M2 polarization was abrogated by miR-20b-5p inhibition. YTHDF1 activated the NF-κB pathway by increasing TIMP2 mRNA stability and expression. circPTP4A2 downregulation promoted microglia M2 polarization to inhibit IS development by regulating the miR-20b-5p/YTHDF1/TIMP2/NF-κB axis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study aimed to explore metabolic abnormalities in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) for metabolism-related genes., Methods: We downloaded expression data for metabolism-related genes, performed differential expression analysis, and applied weighted gene co-expression network analysis (WGCNA) to identify metabolism-related functional modules. We obtained normalised miRNA expression data and identified master methylation regulators for metabolism-related genes. Cox regression of data on metabolism-related genes was performed to screen for genes that affect the prognosis of patients with CESC. Furthermore, we selected key genes for validation., Results: Our results identified 3620 metabolism-related genes in CESC, 2493 of which contained related mutations. The co-occurrence of CUBN, KALRN, and HERC1 was related to the prognosis of CESC. The fraction of genome altered (FGA) closely correlated with overall survival. In expression analysis, 374 genes were related to the occurrence and prognosis of CESC. We then identified four metabolic pathway modules in WGCNA. Further analysis revealed that glycolysis/gluconeogenesis was related to endothelial cells and that arachidonic acid metabolism was related to cell proliferation. These four modules were also related to the prognosis of CESC. Among CESC-related metabolic genes, two genes were found to be regulated by microRNAs (miRNAs) and methylation, whereas another two genes were coregulated by miRNAs and mutations., Conclusions: Among metabolism-related genes, 15 genes were related to the prognosis of CESC. The co-occurrence of CUBN/KALRN/HERC1 was associated with CESC prognosis. Glycolysis/gluconeogenesis was related to endothelial cells, and arachidonic acid metabolism was related to cell proliferation., (© 2023. The Author(s).)

Background: Long non-coding RNAs (lncRNAs) play critical roles in various biological processes in plants. Extensive studies utilizing high-throughput RNA sequencing have revealed that many lncRNAs are involved in plant disease resistance. Oryza sativa RNase P protein 30 (OsRpp30) has been identified as a positive regulator of rice immunity against fungal and bacterial pathogens. Nevertheless, the specific functions of lncRNAs in relation to OsRpp30-mediated disease resistance in rice remain elusive., Results: We conducted a comprehensive analysis of lncRNAs, miRNAs, and mRNAs expression patterns in wild type (WT), OsRpp30 overexpression (OsRpp30-OE), and OsRpp30 knockout (OsRpp30-KO) rice plants. In total, we identified 91 differentially expressed lncRNAs (DElncRNAs), 1671 differentially expressed mRNAs (DEmRNAs), and 41 differentially expressed miRNAs (DEmiRNAs) across the different rice lines. To gain further insights, we investigated the interaction between DElncRNAs and DEmRNAs, leading to the discovery of 10 trans- and 27 cis-targeting pairs specific to the OsRpp30-OE and OsRpp30-KO samples. In addition, we constructed a competing endogenous RNA (ceRNA) network comprising differentially expressed lncRNAs, miRNAs, and mRNAs to elucidate their intricate interplay in rice disease resistance. The ceRNA network analysis uncovered a set of gene targets regulated by lncRNAs and miRNAs, which were found to be involved in pathogen recognition, hormone pathways, transcription factor activation, and other biological processes related to plant immunity., Conclusions: Our study provides a comprehensive expression profiling of lncRNAs, miRNAs, and mRNAs in a collection of defense mutants in rice. To decipher the putative functional significance of lncRNAs, we constructed trans- and cis-targeting networks involving differentially expressed lncRNAs and mRNAs, as well as a ceRNA network incorporating differentially expressed lncRNAs, miRNAs, and mRNAs. Together, the findings from this study provide compelling evidence supporting the pivotal roles of lncRNAs in OsRpp30-mediated disease resistance in rice., (© 2023. The Author(s).)

The symptoms of Behçet's disease (BD), a multisystemic condition with autoimmune and inflammation as hallmarks, include arthritis, recurring oral and vaginal ulcers, skin rashes and lesions, and involvement of the nervous, gastrointestinal, and vascular systems. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), may be important regulators of inflammation and autoimmune disease. These ncRNAs are essential to the physiological and pathophysiological disease course, and miRNA in particular has received significant attention for its role and function in BD and its potential use as a diagnostic biomarker in recent years. Although promising as therapeutic targets, miRNAs must be studied further to fully comprehend how miRNAs in BD act biologically., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gu, Huang, Huang, Zhao, Zheng, Wang and Chen.)

To explore the underlying mechanism of lncRNA MALAT1 in the pathogenesis of diabetic cardiomyopathy (DCM). DCM models were confirmed in db/db mice. MiRNAs in myocardium were detected by miRNA sequencing. The interactions of miR-185-5p with MALAT1 and RhoA were validated by dual-luciferase reporter assays. Primary neonatal cardiomyocytes were cultured with 5.5 or 30 mmol/L D-glucose (HG) in the presence or absence of MALAT1-shRNA and fasudil, a ROCK inhibitor. MALAT1 and miR-185-5p expression were determined by real-time quantitative PCR. The apoptotic cardiomyocytes were evaluated using flow cytometry and TUNEL staining. SOD activity and MDA contents were measured. The ROCK activity, phosphorylation of Drp1 S616 , mitofusin 2 and apoptosis-related proteins were analysed by Western blotting. Mitochondrial membrane potential was examined by JC-1. MALAT1 was significantly up-regulated while miR-185-5p was down-regulated in myocardium of db/db mice and HG-induced cardiomyocytes. MALAT1 regulated RhoA/ROCK pathway via sponging miR-185-5p in cardiomyocytes in HG. Knockdown of MALAT1 and fasudil all inhibited HG-induced oxidative stress, and alleviated imbalance of mitochondrial dynamics and mitochondrial dysfunction, accompanied by reduced cardiomyocyte apoptosis. MALAT1 activated the RhoA/ROCK pathway via sponging miR-185-5p and mediated HG-induced oxidative stress, mitochondrial damage and apoptosis of cardiomyocytes in mice., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Ischemic stroke is caused by insufficient blood supply to the brain. It has acute onset, often disturbance of consciousness, and high mortality and disability rate. However, relationship between ribosomal proteins (RP)-S15 and mitochondrial ribosomal proteins (MRP)-S27 and ischemic stroke remains unclear. The ischemic stroke datasets GSE22255, GSE16561, and GSE199435 were downloaded from gene expression omnibus generated by GPL6883, GPL11154, and GPL570. Differentially expressed genes (DEGs) were screened, and the construction and analysis of protein-protein interaction network, functional enrichment analysis and gene set enrichment analysis were performed. The gene expression heat map was drawn. Comparative toxicogenomics database analysis were performed to find the disease most related to core gene. TargetScan screened miRNAs that regulated central DEGs. Five hundred DEGs were identified. According to gene ontology analysis, they were mainly enriched in leukocyte activation, myoid cell activation involved in immune response, cell membrane, mitochondria, secretory vesicles, catalytic activity, enzyme binding, ribonucleic acid binding, splicing. Gene set enrichment analysis showed that the enrichment items are similar to the enrichment items of differentially expressed genes. And 20 core genes were obtained. Comparative toxicogenomics database analysis showed that 6 genes (RPS15, RPS2, RPS3, MRPS27, POLR2A, MRPS26) were found to be associated with chemical and drug-induced liver injury, necrosis, delayed prenatal exposure, nephropathy, hepatomegaly and tumor. RPS15 and MRPS27 are the core genes of ischemic stroke and play an important role in ischemic stroke., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Colon cancer is a widespread life-threatening malignancy with complex and multifactorial etiology. Both epidemiological cohort studies and basic research support the substantial role of iron metabolism in colon cancer. Thus, understanding the mechanisms of how essential iron metabolic proteins are dysregulated may provide new treatment strategies for colon cancer. Ferritin is the main iron storage protein that occupies a vital position in iron metabolism. Studies reported that ferritin is differentially highly expressed in tissues from multiple malignancies. However, the source and function of highly expressed ferritin in colon cancer have not been explored. In this study, we found that the protein level but not RNA level of ferritin heavy chain (FTH1) was upregulated in colon cancer using paired clinical samples. Co-culture system was used to mimic the in vivo circumstance and study the cell-cell communication of macrophages and colon cancer cells. Results showed that M2 macrophages could substantially increase the FTH1 levels in colon cancer cells. This effect could be blocked by the exosome biogenesis/ secretion inhibitor GW4869, implying the vital role of exosomes in this biological process. Besides, we found that purified exosomes from M2 macrophages could deliver FTH1 into colon cancer cells and promote cell proliferation. Furtherly, EdU assay and live cell imaging system were performed in FTH1-OE (overexpression) colon cancer cell lines and confirmed the cell proliferation promoting effect of FTH1. Our results unveil the source and function of highly expressed FTH1 in colon cancer and provide a new potential therapeutic target for the treatment of colon cancer., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The remodeling of uterine spiral arteries is a complex process requiring the dynamic action of various cell types. During early pregnancy, extravillous trophoblast (EVT) cells differentiate and invade the vascular wall, replacing the vascular smooth muscle cells (VSMCs). Several in vitro studies have shown that EVT cells play an important role in promoting VSMC apoptosis, however, the mechanism underlying this process is not fully understood. In this study, we demonstrated that EVT-conditioned media and EVT-derived exosomes could induce VSMC apoptosis. Through data mining and experimental verification, it was demonstrated that the EVT exosome miR-143-3p induced VSMC apoptosis in both VSMCs and a chorionic plate artery (CPA) model. Furthermore, FAS ligand was also expressed on the EVT exosomes and may play a co-ordinated role in apoptosis induction. These data clearly demonstrated that VSMC apoptosis is mediated by EVT-derived exosomes and their cargo of miR-143-3p as well as their cell surface presentation of FASL. This finding increases our understanding of the molecular mechanisms underlying the regulation of VSMC apoptosis during spiral artery remodeling., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

MicroRNAs (miRNAs) play a crucial role in maintaining the balance between the rapid growth and suppression of tumorigenesis during antler regeneration. This study investigated the role of a novel miRNA, PC-3p-2869 (miR-PC-2869), in antler growth and its therapeutic potential in human osteosarcoma and chondrosarcoma. Stem-loop RT-qPCR showed that miR-PC-2869 was expressed extensively in diverse layers of antler tissues. Overexpression of miR-PC-2869 suppressed the proliferation and migration of antler cartilage cells. Similarly, heterologous expression of miR-PC-2869 reduced the proliferation, colony formation, and migration of osteosarcoma cell line MG63 and U2OS and chondrosarcoma cell line SW1353. Moreover, 18 functional target genes of miR-PC-2869 in humans were identified based on the screening of the reporter library. Among them, 15 target genes, including CDK8, EEF1A1, and NTN1, possess conserved miR-PC-2869-binding sites between humans and red deer ( Cervus elaphus ). In line with this, miR-PC-2869 overexpression decreased the expression levels of CDK8, EEF1A1, and NTN1 in MG63, SW1353, and antler cartilage cells. As expected, the knockdown of CDK8, EEF1A1, or NTN1 inhibited the proliferation and migration of MG63, SW1353, and antler cartilage cells, demonstrating similar suppressive effects as miR-PC-2869 overexpression. Furthermore, we observed that CDK8, EEF1A1, and NTN1 mediated the regulation of c-myc and cyclin D1 by miR-PC-2869 in MG63, SW1353, and antler cartilage cells. Overall, our work uncovered the cellular functions and underlying molecular mechanism of antler-derived miR-PC-2869, highlighting its potential as a therapeutic candidate for bone cancer.

Pathological cardiac hypertrophy is one of the notable causes of heart failure. Circular RNAs (circRNAs) have been studied in association with cardiac hypertrophy; however, the mechanisms by which circRNAs regulate cardiac hypertrophy remain unclear. In this study, we identified a new circRNA, named circCacna1c, in cardiac hypertrophy. Adult male C57BL/6 mice and H9c2 cells were treated with isoprenaline hydrochloride (ISO) to establish a hypertrophy model. We found that circCacna1c was upregulated in ISO-induced hypertrophic heart tissue and H9c2 cells. Western blot and quantitative real-time polymerase chain reaction showed that silencing circCacna1c inhibited hypertrophic gene expression in ISO-induced H9c2 cells. Mechanistically, circCacna1c competitively bound to miR-29b-2-5p in a dual-luciferase reporter assay, which was downregulated in ISO-induced hypertrophic heart tissue and H9c2 cells. MiR-29b-2-5p inhibited the nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) to control hypertrophic gene expression. After silencing circCacna1c, the expression of miR-29b-2-5p increased, which reduced hypertrophic gene expression by inhibiting NFATc1 expression. Together, these experiments indicate that circCacna1c promotes ISO-induced pathological hypertrophy through the miR-29b-2-5p/NFATc1 axis.

Background: Olfactory ensheathing cells (OECs) serve as a bridge by migrating at the site of spinal cord injury (SCI) to facilitate the repair of the neural structure and neural function. However, OEC migration at the injury site not only faces the complex and disordered internal environment but also is closely associated with the migration ability of OECs., Methods: We extracted OECs from the olfactory bulb of SD rats aged <7 days old. We verified the micro ribonucleic acid (miR)-145a-5p expression level in the gene chip after SCI and OEC transplantation using quantitative reverse transcription (qRT)-polymerase chain reaction (PCR). The possible target gene Plexin-A2 of miR-145a-5p was screened using bioinformatics and was verified using dual-luciferase reporter assay, Western blot, and qRT-PCR. The effect of miR-145a-5p/plexin-A2 on OEC migration ability was verified by wound healing assay, Transwell cell migration assay, and immunohistochemistry. Nerve repair was observed at the injured site of the spinal cord after OEC transplantation using tissue immunofluorescence and magnetic resonance imaging, diffusion tensor imaging, and the Basso-Beattie-Bresnahan locomotor rating scale were further used for imaging and functional evaluation., Results: miR-145a-5p expression in the injured spinal cord tissue after SCI considerably decreased, while Plexin-A2 expression significantly increased. OEC transplantation can reverse miR-145a-5p and Plexin-A2 expression after SCI. miR-145a-5p overexpression enhanced the intrinsic migration ability of OECs. As a target gene of miR-145a-5p, Plexin-A2 hinders OEC migration. OEC transplantation overexpressing miR-145a-5p after SCI can increase miR-145a-5p levels in the spinal cord, reduce Plexin-A2 expression in the OECs and the spinal cord tissue, and promote OEC migration and distribution at the injured site. OEC transplantation overexpressing miR-145a-5p can promote the repair of neural morphology and neural function., Conclusions: Our study demonstrated that miR-145a-5p could promote OEC migration by down-regulating the target gene Plexin-A2, and transplantation of miR-145a-5p engineered OECs was beneficial to enhance neural structural and functional recovery in SCI rats., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Silica nanoparticles (SiNPs) could cause damage to spermatogenesis, and microRNAs were reported to be associated with male reproduction. This research was designed to explore the toxic impacts of SiNPs induced in male reproduction through miR-5622-3p. In vivo, 60 mice were randomized into the control group and SiNPs group, in which they were exposed to SiNPs for 35 days and then recovered for 15 days. In vitro, 4 groups were set: control group, SiNPs group, SiNPs + miR-5622-3p inhibitor group, and SiNPs + miR-5622-3p inhibitor negative control (NC) group. Our research indicated SiNPs caused the apoptosis of spermatogenic cells, increased level of γ-H2AX, raised the expressions of RAD51, DMC1, 53BP1, and LC8 which were DNA damage repair relative factors, and upregulated Cleaved-Caspase-9 and Cleaved-Caspase-3 levels. Furthermore, SiNPs also elevated the expression of miR-5622-3p but downregulated the level of ZCWPW1. However, miR-5622-3p inhibitor reduced the level of miR-5622-3p, increased the level of ZCWPW1, relieved DNA damage, and depressed the activation of apoptosis pathway, thus, alleviating spermatogenic cells apoptosis caused by SiNPs. The above-mentioned results indicated that SiNPs induced DNA damage resulting in activating of DNA damage response. Meanwhile, SiNPs raised the level of miR-5622-3p targeting inhibited expression of ZCWPW1 to suppress the repair process, possibly making DNA damage so severe that leading to the failure of DNA damage repair, finally inducing the apoptosis of spermatogenic cells.

Cancer has become the most common life-threatening disease in the world. Cancers presenting with advanced stages and metastasis show poor prognosis, even with the application of radiotherapy, surgery, chemotherapy and immunotherapy. It is of great importance to explore novel, efficient biomarkers and their internal mechanisms. Recently, it has been reported that long noncoding RNAs (lncRNAs) play important roles in tumor initiation and progression, influencing downstream mRNAs by interacting with miRNAs and functioning as sponges in competing endogenous RNA (ceRNA) networks. Small nucleolar RNA host gene 9 (SNHG9) binds with miRNAs, inducing miRNA downregulation. The downregulated miRNAs enhance downstream target gene expression via ceRNA networks. Dysregulation of SNHG9 is widely observed in tumors and is associated with clinical prognosis features, which makes it a valuable target for cancer biomarkers and therapeutics. Dysregulated SNHG9 in tumor cells also functions in tumor proliferation, colony formation, migration, invasion and inhibition of apoptosis and tumor cell metabolism. This systematic review of SNHG9 in tumors provides new perspectives on cancer diagnosis and treatment., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Long non-coding RNAs are thought to play a vital role in a variety of human malignancies. Studies have shown that MIR155 host gene (MIR155HG) acts as an oncogene in several cancers, but the function and its mechanism of MIR155HG in gastric cancer (GC) is still poorly understood. In this study, we determined the biological functions and underlying mechanisms of MIR155HG in GC cells. We found that expression levels of MIR155HG was increased markedly in GC patients' serum. In vitro and in vivo studies demonstrated that MIR155HG modulated the malignant phenotype of GC cells, such as cell proliferation, colony forming ability, cell migration ability, and tumor growth in nude mice. Next, our results revealed that NF-κB and STAT3 signaling pathways could be involved in regulating the malignant behavior of GC cells. Our rescue experiments showed that inhibiting NF-κB and STAT3 signaling pathways attenuated the phenotypes caused by MIR155HG overexpression. Moreover, cytotoxicity and apoptosis assays revealed overexpression of MIR155HG reduced the apotosis of GC cells induced by cisplatin and 5-FU. Together, our studies suggested that MIR155HG overexpression promoted proliferation, migration, and chemoresistance of GC cells. These results might provide a lncRNA-based target for GC treatment in future., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The capability of microRNAs (miRNAs) to regulate gene expression across species has opened new avenues for miRNA-based therapeutics. Here, we investigated the potential of PC-5p-1090 (miR-PC-1090), a miRNA found in deer antlers, to control the malignant phenotypes of hepatocellular carcinoma (HCC) cells. Using Cell Counting Kit-8 and transwell assays, we found that heterologous expression of miR-PC-1090 inhibited HCC cell proliferation, migration, and invasion. Bioinformatics analysis indicated that predicted miR-PC-1090 targets, including MARCKS, SMARCAD1, and SOX9, were significantly elevated in HCC tissues, and their high expressions were associated with poor overall survival of HCC patients. Moreover, mechanistic investigations revealed that miR-PC-1090 promoted the degradation of MARCKS and SMARCAD1 mRNAs and hindered the translation of SOX9 mRNA by recognizing their 3' untranslated regions. Subsequent loss-of-function and rescue experiments confirmed the involvement of MARCKS, SMARCAD1, and SOX9 in miR-PC-1090-suppressed HCC cell proliferation, migration, and invasion. Notably, MARCKS knockdown induced the downregulation of phosphorylated MARCKS and a corresponding upregulation of phosphorylated AKT in HCC. Conversely, miR-PC-1090 repressed MARCKS phosphorylation and effectively circumvented the activation of the PI3K/AKT pathway. Furthermore, miR-PC-1090 regulates the Wnt/β-catenin pathway through SMARCAD1- and SOX9-mediated reduction of β-catenin expression. Overall, our results illustrate the tumor-suppressive activity and molecular mechanism of antler-derived miR-PC-1090 in HCC cells, indicating its potential as a multiple-target agent for HCC treatment., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

As a major apurinic/apyrimidinic endonuclease and a redox signaling protein in human cells, APE1 plays a crucial role in cellular function and survival. The relationship between alterations of APE1 expression and subcellular localization and the initiation, development and treatment of various cancers has received extensive attention. However, comparing the in-vivo activity of APE1 in normal and cancerous breast live cells remains challenging due to the low efficiency of commonly used liposome transfection methods in delivering DNA substrate probes into human normal breast epithelial cells (MCF-10A). In this work, we develop a DNA/RNA hybrid-based small magnetic fluorescent nanoprobe (25 ± 3 nm) that can be taken up by various live cells under magnetic transfection. The D 0 /R-nanoprobe demonstrates an outstanding specificity toward APE1 and strong resistance to the cellular background interference. Using this nanoprobe, we are not only able to visualize the intracellular activity of APE1 in breast ductal carcinoma (MCF-7) live cells, but also demonstrate the APE1 activity in MCF-10A live cells for the first time. The method is then extended to observe the changes in APE1 levels in highly metabolically active neuroendocrine cells under normal conditions and severe attacks by reactive oxygen species in real-time. The fluorescent nanoprobe provides a useful tool for studying the dynamic changes of intracellular APE1 in normal or cancerous live cells. It also displays the potential for visible and controllable release of miRNA drugs within live cells for therapeutic purposes.

MicroRNAs (miRNAs) are known to be important post-transcriptional regulators of gene expression and have been shown to be associated with insecticide resistance in insects. In this research, we show that a miRNA, PC-5p-30&#95;205949, is involved in triflumezopyrim susceptibility via regulating expressive abundance of cytochrome P450 CYP419A1 and ATP-binding cassette transporters ABCG23 in the small brown planthopper (SBPH), Laodelphax striatellus (Fallén). Triflumezopyrim treatment significantly reduced the abundance of PC-5p-30&#95;205949, feeding of agomir-PC-5p-30&#95;205949 significantly increased the sensitivity of SBPH to triflumezopyrim, and its spatiotemporal expression profiles showed that PC-5p-30&#95;205949 were expressed at all developmental stages and were highly expressed in head tissue. By software prediction and dual luciferase reporter assay, the target genes of PC-5p-30&#95;205949 were identified as two detoxification metabolism genes CYP419A1 and ABCG23. The relative expressions of CYP419A1 and ABCG23 were significantly up-regulated after 24 h, 48 h and 72 h with triflumezopyrim exposure. CYP419A1 was highly expressed in the 4th-instar nymphs and male adults, with the highest expression level in fat body. ABCG23 was highly expressed in female adults, and had the highest expression in head. Furthermore, silencing of CYP419A1 and ABCG23 by RNA interference significantly increased the mortality of SBPH to triflumezopyrim, and molecular docking showed that CYP419A1 and ABCG23 could stably bind to triflumezopyrim with binding free energies of -171.5622 and - 103.3402 kcal mol -1 , respectively. These results suggest that SBPH has a strategy to enhance the resistance to triflumezopyrim by attenuating the expression of PC-5P-30&#95;205949, thereby activating the detoxification metabolic pathway by targeting CYP419A1 and ABCG23., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Preeclampsia (PE) is a common complication of pregnancy, usually accompanied by symptoms such as hypertension and proteinuria. It can induce severe conditions that may result in maternal and fetal morbidity and fatality. In this study, we use bioinformatics analysis to compare microRNA microassay in decidual stromal cells from PE patients and healthy donors. Our result indicated that placentas from PE patients had a higher CCL1/CXCL2 expression, compared with those from healthy donors. Bioinformatics analysis confirmed that decidual stromal cells derived from PE patients expressed significantly lower miR-455-3p than those derived from healthy donors. Transfection of miR-455-3p inhibitors enhanced the CCL2/CXCL8 expression in decidual stromal cells, and luciferase activity assay confirmed that nuclear factor of activated T cells 5 (NFAT5) mRNA was the direct target of miR-455-3p; NFAT5 also promoted cytokine secretion. In the flow cytometry study, higher M1 macrophage infiltration was observed in placentas from PE patients than in those from healthy donors. We also observed that condition medium (CM) derived from decidual stromal cells could significantly promote M1 polarization of macrophages after transfection with miR-455-3p inhibitor; further, transwell invasion assay confirmed that decidual stromal cells-CM educated macrophages suppressed trophoblast invasion. Taken together, our result demonstrates that downregulation of miR-455-3p in decidual stromal cells can promote macrophage polarization and suppress trophoblasts invasion., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: MicroRNAs (miRNAs) are endogenous noncoding single-stranded small RNAs. Numerous studies have shown that miRNAs have pivotal roles in the occurrence and development of myocardial fibrosis (MF). However, miRNA expression profile in rats with MF after myocardial infarction (MI) is not well understood. The present study aimed to find the potential miRNA for MF post MI., Methods: SPF male Sprague-Dawley (SD) rat models of acute myocardial infarction (AMI) were established by ligating the anterior descending branch of the left coronary artery, while sham-operated rats were only threaded without ligation as a control group. Hematoxylin-eosin and Masson trichrome staining were used to detect myocardial histopathological changes for model evaluation. The differentially expressed miRNAs were detected by using the Agilent Rat miRNA gene chip in the myocardial tissue of the infarct marginal zone. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by DAVID. The expression of miR-199a-5p was verified by real-time fluorescence quantitative PCR (qRT-PCR). Transfected miR-199a-5p mimics into cardiac fibroblasts (CFs) to construct cell models of miR-199a-5p overexpression. Dual-luciferase reporter assay was employed to validate the target gene of miR-199a-5p. The protein expression of the target gene in CFs transfected with miR-199a-5p mimics were detected by Western blot., Results: Myocardial fibrosis was exacerbated in the model group compared with the control group. Thirteen differentially expressed miRNAs between the two groups were screened and their expression levels in the model group were all higher than those in the control group. The expression of miR-199a-5p was significantly increased in the model group in qRT-PCR, which was consistent with the results of the gene chip. KEGG enrichment analysis showed that the target genes of miR-199a-5p were enriched in the insulin signaling pathway. Furthermore, dual-luciferase reporter assay indicated that miR-199a-5p could negatively regulate the expression of GSK-3β. After transfection, the expression of miR-199a-5p was increased in the miR-199a-5p mimics group. The protein expression of GSK-3β was decreased in CFs transfected with miR-199a-5p mimics., Conclusion: Our study identified miR-199a-5p could promote the progression of myocardial fibrosis after myocardial infarction by targeting GSK-3β, which provides novel targets for diagnosis and treatment of MF., Competing Interests: The authors declare there are no competing interests., (© 2023 Guo et al.)

Aims: Since the inhibitory effect of KNG1 on glioma has been proved, this study further explores the regulation of the lncRNA/miRNA axis on KNG1 in glioma., Methods: The miRNAs that target KNG1 and the lncRNA that targets miR-942-5p were predicted by bioinformatics analysis and verified by experiments. The correlations between miR-942-5p and the survival of patients and between KNG1 and miR-942-5p were analyzed. After transfection, cell migration, invasion, proliferation, and cell cycle were detected through wound healing, Transwell, colony formation, and flow cytometry assays. A mouse subcutaneous xenotransplanted tumor model was established. The expressions of miR-942-5p, KNG1, LINC01018, and related genes were evaluated by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR), Western blot, or immunohistochemistry., Results: MiR-942-5p targeted KNG1, and LINC01018 sponged miR-942-5p. The high survival rate of patients was related to low miR-942-5p level. MiR-942-5p was highly expressed, whereas KNG1 was lowly expressed in glioma. MiR-942-5p was negatively correlated with KNG1. Silent LINC01018 or KNG1 and miR-942-5p mimic enhanced the migration, invasion, and proliferation of glioma cells, and regulated the expressions of metastasis-related and proliferation-related genes. LINC01018 knockdown and miR-942-5p mimic promoted glioma tumor growth in mice. The levels of miR-942-5p and KNG1 were decreased by LINC01018 knockdown, and LINC01018 expression was suppressed by miR-942-5p mimic. MiR-942-5p inhibitor, KNG1, and LINC01018 had the opposite effect to miR-942-5p mimic., Conclusion: LINC01018/miR-942-5p/KNG1 pathway regulates the development of glioma cells in vitro and in vivo., (© 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Results of previous studies suggested that renal fibrosis and epithelial-mesenchymal transition (EMT) plays an important role in the process of renal fibrosis, but the underlying mechanism remains unclear. Long coding RNA (lncRNA) CRNDE has emerged as potent regulators of EMT programs, therefore, in present work, we examined the roles of LncRNA CRNDE/miR-29a-3p axis in renal fibrosis and the underlying mechanism. We found that in both renal fibrosis animal and cell models, lncRNA CRNDE was dynamically upregulated in animal models or cells by the treatment of TGF-β. Furthermore, knockdown of CRNDE to rat significantly inhibited EMT, prevented renal fibrosis. Finally, CRNDE regulates renal fibrosis through suppression of miR-29a-3p expression. Together, our results demonstrated that CRNDE acted as a regulator of renal fibrosis via targeting miR-29a-3p. Our findings may provide a potential therapeutic target for the treatment of renal fibrosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract: Background: Acute lung injury (ALI) induced by sepsis is distinguished by an inflammatory progression. Herein, we investigated the action of circular RNA kelch like family member 2 (circKlhl2) in sepsis-induced ALI. Methods: The animal or cell model of sepsis ALI was established by LPS stimulation. The contents of circKlhl2, microRNA-29b-3p (miR-29b-3p), rho-associated coiled-coil containing protein kinase 1 (ROCK1), CyclinD1, B-cell lymphoma-2 (Bcl-2), and cleaved-caspase 3 (C-caspase-3) were detected by quantitative real-time polymerase chain reaction and western blot, respectively. Cell viability was assessed by cell counting kit 8 assay. Cell cycle and apoptosis were evaluated by flow cytometry. The abundances of proinflammatory cytokines were detected by enzyme-linked immunosorbent assay. Besides, the targeted relationship between miR-29b-3p and circKlhl2 or ROCK1 was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Results: Loss of circKlhl2 mitigated lung injury and proinflammatory cytokine expression in sepsis-ALI mice model and alleviated LPS-induced apoptosis and inflammatory response in microvascular endothelial cell (MPVECs) in vitro . The abundances of circKlhl2 and ROCK1 were boosted, while the miR-29b-3p level was diminished in the animal or cell model of sepsis-ALI. MiR-29b-3p inhibition abrogated circKlhl2 knockdown-mediated effects on MPVECs injury. Moreover, miR-29b-3p overexpression promoted cell proliferation and inhibited apoptosis and inflammation in LPS-treated MPVECs, while ROCK1 enhancement reversed these effects. Conclusion: CircKlhl2 expedited the sepsis-induced ALI by adjusting miR-29b-3p/ROCK1 axis., Competing Interests: The authors report no conflicts of interests., (Copyright © 2022 by the Shock Society.)