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Objective: This study aimed to examine the role of long non-coding RNA PCED1B antisense RNA 1 (PCED1B-AS1) in the development of hepatocellular carcinoma (HCC)., Methods: A total of 62 pairs of HCC tissues and adjacent non-tumor tissues were obtained from 62 HCC patients. The interactions of PCED1B-AS1 and microRNA-34a (miR-34a) were detected by dual luciferase activity assay and RNA pull-down assay. The RNA expression levels of PCED1B-AS1, miR-34a and CD44 were detected by RT-qPCR, and the protein expression level of CD44 was determined by Western blotting. The cell proliferation was detected by cell proliferation assay, and the cell invasion and migration by transwell invasion assay. The HCC tumor growth after PCED1B-AS1 was downregulated was determined by in vivo animal study., Results: PCED1B-AS1 was highly expressed in HCC tissues, which was associated with poor survival of HCC patients. Furthermore, PCED1B-AS1 interacted with miR-34a in HCC cells, but they did not regulate the expression of each other. Additionally, PCED1B-AS1 increased the expression level of CD44, which was targeted by miR-34a. The cell proliferation and invasion assay revealed that miR-34a inhibited the proliferation and invasion of HCC in vitro, while CD44 exhibited the opposite effects. Furthermore, PCED1B-AS1 suppressed the role of miR-34a. Moreover, the knockdown of PCED1B-AS1 repressed the HCC tumor growth in nude mice in vivo., Conclusion: PCED1B-AS1 may play an oncogenic role by regulating the miR-34a/CD44 axis in HCC., (© 2024. Huazhong University of Science and Technology.)

Geosmin is an environmental pollutant that causes off-flavor in water and aquatic products. The high occurrence of geosmin contamination in aquatic systems and aquaculture raises public awareness, however, few studies have investigated the response pathways of geosmin stress on freshwater fish. In this research, grass carp were exposed to 50 μg/L geosmin for 96 h, liver tissue was sequenced and validated using real-time qPCR. In total of 528 up-regulated genes and 488 down-regulated genes were observed, includes cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase related genes. KEGG analysis showed that chemical carcinogenesis-DNA adducts, metabolism of xenobiotics by cytochrome P450, drug metabolism-cytochrome P450 pathway was enriched. Common genes from the target genes of microRNAs and differential expression genes are enriched in metabolism of xenobiotics cytochrome P450 pathway. Two miRNAs (dre-miR-146a and miR-212-3p) down regulated their target genes (LOC127510138 and adh5, respectively) which are enriched cytochrome P450 related pathway. The results present that geosmin is genetoxic to grass carp and indicate that cytochrome P450 system and UDP-glucuronosyltransferase play essential roles in biotransformation of geosmin. MicroRNAs regulate the biotransformation of geosmin by targeting specific genes, which contributes to the development of strategies to manage its negative impacts in both natural and artificial environments., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neuroinflammation in the spinal cord following acute brachial plexus injury (BPI) remains a vital cause that leads to motor dysfunction and neuropathic pain. In this study, we aim to explore the role of long non-coding RNA JHDM1D antisense 1 (JHDM1D-AS1) in mediating BPI-induced neuroinflammation and neuronal injury., Methods: A total brachial plexus root avulsion (tBPRA) model in adult rats and IL-1β-treated motor neuron-like NSC-34 cells and LPS-treated microglia cell line BV2 were conducted for in vivo and in vitro experiments, respectively. The expressions of JHDM1D-AS1, miR-101-3p and DUSP1, p38, NF-κB, TNF-α, IL-1β, and IL-6 were detected by RT-PCR and western blot seven days after tBPI. Immunohistochemistry (IHC) was used to detect neuronal apoptosis. CCK8 assay, Tunel assay and LDH kit were used for the detection of neuronal injury. The targeted relationships between JHDM1D-AS1 and miR-101-3p, miR-101-3p and DUSP1 were verified by RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assay., Results: We found significant downregulated expression of JHDM1D-AS1 and DUSP1 but upregulated expression of miR-101-3p in the spinal cord after tBPI. Overexpression of JHDM1D-AS1 had a prominent neuroprotective effect by suppressing neuronal apoptosis and microglial inflammation through reactivation of DUSP1. Further exploration revealed that JHDM1D-AS1 may act as a competitive endogenous RNA targeting miR-101-3p, which bound on the 3'UTR of DUSP1 mRNA. In addition, overexpression of miR-101-3p could reverse the neuroprotective effects of JHDM1D-AS1 upregulation by blocking DUSP1., Conclusions: JHDM1D-AS1 exerted neuroprotective and anti-inflammatory effects in a rat model of tBPI by regulating miR-101-3p/DUSP1 axis., (Copyright © 2020. Published by Elsevier B.V.)

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) has been implicated in human cancers, but its role and clinical significance in hepatocellular carcinoma (HCC) remain unknown. Here, we show that HMGCS2 is downregulated and exhibits antimetastatic potential in HCC. Low expression of HMGCS2 was associated with poor tumor differentiation, vascular invasion and worse overall and disease-free survivals in two independent cohorts consisting of 743 cases. In vitro data demonstrated HMGCS2 overexpression suppressed, whereas HMGCS2 silence promoted HCC cell migration via Epithelial-Mesenchymal Transition (EMT) process and the activation of ERK/c-Jun signaling pathway. Inhibition of ERK phosphorylation by PD098059 markedly attenuated the malignant phenotypes mediated by HMGCS2 siRNA. Furthermore, miR-107 was identified as an upstream regulator of HMGCS2 via directly targeting the 3'-UTR of HMGCS2 mRNA. Collectively, our findings suggest HMGCS2 serve as a promising prognostic biomarker and exert anti-tumor activity towards HCC, and therefore provide a potential target for HCC clinical intervention., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objectives: miR-200a has been established as a key regulator of HSC activation processes in liver fibrosis. Epigenetic silencing of miR-200a contributing to SIRT1 over-expression has been discussed in breast cancer; however, whether miR-200a controls SIRT1 gene expression in hepatic fibrosis is still unknown., Methods and Materials: We analyzed miR-200a regulation of SIRT1 expression in CCl 4 -induced liver fibrosis and TGF-β1-mediated activation of HSC. miR-200a, SIRT1, α-SMA, Col1A1, Notch1 and NICD expression were estimated by Western blotting, qRT-PCR and Immunohistochemistry. HSCs were transfected with miR-200a mimic, miR-200a inhibitor and SIRT1-RNAi. Luciferase reporter assays further confirmed the interaction between miR-200a and the SIRT1 mRNA 3'-UTR. Cell proliferation ability was assessed by MTT and cell cycle., Results: We found that treatment activated HSC with miR-200a mimics, restored miR-200a expression and reduced SIRT1 levels. Conversely, treatment activated HSC with miR-200a inhibitors, decreased miR-200a expression and up-regulated SIRT1 levels. Restoration of miR-200a or the knockdown of SIRT1 prevented HSC activation and proliferation. We have established the SIRT1 transcript as subject to regulation by miR-200a, through miR-200a targeting of SIRT1 3'-UTR. Finally, HSC transfected with SIRT1-siRNA increased the levels of Notch1 protein and mRNA expression., Conclusions: Our study demonstrated that miR-200a regulates SIRT1/Notch1 expression during HSC activation and fibrosis.

Background: Recent studies show that microRNA-145 (miRNA-145) might be an attractive tumor biomarker of considerable prognostic value, but little is known about their relationship with acute myocardial infarction (AMI). This study investigated the correlation between the level of miR-145 and AMI., Methods: One-hundred patients were divided into three groups: no coronary artery disease (CAD) group, non-ST segment elevation myocardial infarction group, and ST segment elevation myocardial infarction group. The plasma levels of miR-145 were quantified using real-time quantitative polymerase chain reaction. Logarithmic transformation of miRNA-145 levels (Ln&#95;miRNA-145) was used for statistical analysis due to the skewed data distribution., Results: Plasma levels of miR-145 were significantly lower in patients with AMI compared to patients in the non-CAD group (-6.38 ± 0.11 vs. -4.47 ± 0.17, P< 0.0001). Compared to those without heart failure, the levels of miR-145 were significantly lower in patients with heart failure (-6.91 ± 0.20 vs. -5.35 ± 0.13, P< 0.0001). We also found that the lower plasma levels of miRNA-145 significantly correlated with increased serum levels of B-type natriuretic peptide (Spearman ρ= -0.60, P< 0.0001), troponin T (Spearman ρ= -0.62, P< 0.0001), and decreased ejection fraction (Spearman ρ= 0.65, P< 0.0001). In a multivariable linear regression analysis, AMI and heart failure were independently associated with lower Ln&#95;miRNA-145 (estimate -0.99, standard error [SE] 0.28; P= 0.001 and estimate -0.62, SE 0.21; P= 0.004)., Conclusions: Our results suggest that decreased plasma levels of miR-145 are associated with AMI. Circulating miR-145 may be useful in prognosticating cardiac function and the risk of developing heart failure., Competing Interests: There are no conflicts of interest.

We examined the impact of single nucleotide polymorphisms (SNPs) at miRNA binding sites in the 3'-UTRs of genes in the apoptosis pathway on the prognosis of patients with limited disease-small cell lung cancer (LD-SCLC). Twelve tagSNPs in seven genes were genotyped using blood samples from 146 LD-SCLC patients treated with chemoradiotherapy. Cox proportional hazard regression models and recursive partitioning analysis were performed to identify SNPs significantly associated with overall survival. Three SNPs, CASP8: rs1045494 (C > T), PIK3R1: rs3756668 (A > G) and CASP7: rs4353229 (T > C), were associated with longer overall survival in LD-SCLC patients after chemoradiotherapy. The adjusted hazard ratios (95% confidence intervals) were 0.480 (0.258-0.894), 0.405 (0.173-0.947) and 0.446 (0.247-0.802), respectively, and remained significant after multiple comparison correction. Moreover, subset analysis showed these SNPs were still predictive of overall survival in stage III patients. Recursive partitioning analysis enabled patients to be classified into three risk subgroups based on unfavorable genotype combinations of the rs1045494 and rs4353229 SNPs. These findings suggest miRNA-related polymorphisms in the apoptosis pathway may be useful biomarkers for selection of LD-SCLC patients likely to benefit from chemoradiotherapy., Competing Interests: All authors of this manuscript have no conflicts of interest to disclose.

Dysregulation of microRNA contributes to the high incidence and mortality of breast cancer. Here, we show that miR-625 was frequently down-regulated in breast cancer. Decrease of miR-625 was closely associated with estrogen receptor (P = 0.004), human epidermal growth factor receptor 2 (P = 0.003) and clinical stage (P = 0.001). Kaplan-Meier and multivariate analyses indicated miR-625 as an independent factor for unfavorable prognosis (hazard ratio = 2.654, 95% confident interval: 1.300-5.382, P = 0.007). Re-expression of miR-625 impeded, whereas knockdown of miR-625 enhanced cell viabilities and migration abilities in breast cancer cells. HMGA1 was confirmed as a direct target of miR-625. The expressions of HMGA1 mRNA and protein were induced by miR-625 mimics, but reduced by miR-625 inhibitor. Re-introduction of HMGA1 in cells expressing miR-625 distinctly abrogated miR-625-mediated inhibition of cell growth. Taken together, our data demonstrate that miR-625 suppresses cell proliferation and migration by targeting HMGA1 and suggest miR-625 as a promising prognostic biomarker and a potential therapeutic target for breast cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objective: MicroRNAs (miRNAs) have been shown to be associated with various physiological and pathological conditions, including inflammation and cardiovascular disease, but little is known about their relationship with the presence of coronary artery disease (CAD) and disease severity., Methods: A total of 195 consecutive subjects who underwent coronary angiography for chest pain evaluation were enrolled in this study. In CAD patients severity of coronary lesions was assessed by the number of diseased vessels and the Synergy between PCI with Taxus and Cardiac surgery score (SYNTAX score). Plasma levels of miRNA-145 were quantified by real-time quantitative polymerase chain reaction test, and logarithmic transformation of miRNA-145 levels (Ln&#95;miRNA-145) was used for analyses due to its skewed distribution., Results: Of the 195 total subjects 167 patients were diagnosed as having CAD. Ln&#95;miRNA-145 was significantly lower in CAD patients compared with the non-CAD group (-6.11 ± 0.92 vs. -5.06 ± 1.25; p < 0.001). In multivariable linear regression analyses CAD was significantly associated with lower Ln&#95;miRNA-145 (Estimate, -0.50; standard error (SE), 0.11; p < 0.0001). Furthermore, among CAD patients, three-vessel disease, higher SYNTAX scores and STEMI were significantly associated with lower Ln&#95;miRNA-145 ([Estimate, -0.40; SE, 0.07; p < 0.0001]; [Estimate, -0.02, SE, 0.10; p = 0.005] and [Estimate, -0.35, SE, 0.10; p < 0.001] respectively)., Conclusions: Lower plasma levels of miRNA-145 were significantly associated with the presence as well as severity of CAD. As a potential biomarker for CAD, plasma miRNA-145 may be useful in predicting CAD and its severity in patients presenting with chest pain.

Hepatic fibrosis is a common final pathological process in the progression of liver disease, which is primarily due to oxidative stress. Nrf2 is known to coordinate induction of genes that encode antioxidant enzymes. Moreover, Nrf2 expression is largely regulated through the association of Nrf2 with Keap1, which results in cytoplasmic Nrf2 degradation. Conversely, little is known concerning the regulation of Keap1 expression. Although the function of miRNA-200a controls Keap1 gene expression has been discussed in many cancers and fibrotic diseases, its role in hepatic fibrosis is still poorly understood. By using miRNA mimic, we observed miRNA-200a silencing in activated hepatic stellate cell and demonstrated that upon re-expression, miRNA-200a targets the Keap1, and leading to Keap1 mRNA degradation. We find that treatment with miRNA-200a mimics, restored miRNA-200a expression and reduced Keap1 levels. This reduction in Keap1 levels corresponded with Nrf2 nuclear translocation and activation of Nrf2-dependent NQO1 gene transcription. Moreover, we found that Nrf2 activation inhibited the TGF-β1-independent growth of hepatic stellate cell. Finally, our study demonstrates that miRNA-200a regulates the Keap1/Nrf2 pathway in hepatic stellate cell and fibrosis, and we find that epigenetic therapy can restore miRNA-200a regulation of Keap1 expression, therefore reactivating the Nrf2-dependent antioxidant pathway in liver fibrosis., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background and Purpose: MicroRNAs have recently been shown to regulate the downstream bioprocesses of intracerebral hemorrhage. The aim of this study was to investigate whether miRNAs can be used as biomarkers to predict secondary hematoma enlargement (HE) in patients with ICH., Methods: Consecutively, 79 ICH patients admitted within 6 h of symptom onset and 30 healthy individuals were enrolled in this study. Whole-genome miRNA expression profiles were generated in 32 patients (HE/non-HE: 14/18). Representative differentially expressed miRNAs were measured in all cases (HE/non-HE: 30/49) and normal controls (n = 30) by real-time PCR., Results: Thirty miRNAs showed differential expressions in the plasma samples from patients with HE as compared with the non-HE controls. Compared to the hierarchical cluster analysis with all probes on microarray, all patients were separated into two main branches with only four exceptions by 30 differentially expressed miRNAs, improving the overall accuracy from 47.62 to 77.78% in the HE and 72.73 to 100% in the non-HE group. Further support vector machine (SVM) test can discriminate the two groups with 100% accuracy with 10 differentially expressed miRNAs., Conclusions: We demonstrated that multiple miRNAs are differentially expressed in the plasma of ICH patients with or without HE and may serve as circulating biomarkers for predicting HE after ICH., (© 2012 Blackwell Publishing Ltd.)