• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.289-298
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• 2023

Complex diseases including cardiovascular disease are caused by a combination of the alternation of many genes and the influence of environments. Recently, non-coding RNAs (ncRNAs) have been shown to be involved in diverse diseases, and the functions of various ncRNAs have been reported. Many researchers have elucidated the mechanisms of action of these ncRNAs at the cellular level prior to in vivo and clinical studies of the diseases. Due to the characteristics of complex diseases involving intercellular crosstalk, it is important to study communication between multiple cells. However, there is a lack of literature summarizing and discussing studies of ncRNAs involved in intercellular crosstalk in cardiovascular diseases. Therefore, this review summarizes recent discoveries in the functional mechanisms of intercellular crosstalk involving ncRNAs, including microRNAs, long non-coding RNAs, and circular RNAs. In addition, the pathophysiological role of ncRNAs in this communication is extensively discussed in various cardiovascular diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8893-8900
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• 2014

Dysregulated expression of microRNAs (miRNAs) has been shown to be closely associated with tumor development, progression, and carcinogenesis. However, their clinical implications for gastric cancer remain elusive. To investigate the hypothesis that genome-wide alternations of miRNAs differentiate gastric cancer tissues from those matched adjacent non-tumor tissues (ANTTs), miRNA arrays were employed to examine miRNA expression profiles for the 5-pair discovery stage, and the quantitative real-time polymerase chain reaction (qRTPCR) was applied to validate candidate miRNAs for 48-pair validation stage. Furthermore, the relationship between altered miRNA and clinicopathological features and prognosis of gastric cancer was explored. Among a total of 1,146 miRNAs analyzed, 16 miRNAs were found to be significantly different expressed in tissues from gastric cancer compared to ANTTs (p<0.05). qRT-PCR further confirmed the variation in expression of miR-193b and miR-196a in the validation stage. Down-expression of miR-193b was significantly correlated with Lauren type, differentiation, UICC stage, invasion, and metastasis of gastric cancer (p<0.05), while over-expression of miR-196a was significantly associated with poor differentiation (p=0.022). Moreover, binary logistic regression analysis demonstrated that the UICC stage was a significant risk factor for down-expression of miR-193b (adjusted OR=8.69; 95%CI=1.06-56.91; p=0.043). Additionally, Kaplan-Meier survival curves indicated that patients with a high fold-change of down-regulated miR-193b had a significantly shorter survival time (n=19; median survival=29 months) compared to patients with a low fold-change of down-regulated miR-193b (n=29; median survival=54 months) (p=0.001). Overall survival time of patients with a low fold-change of up-regulated miR-196a (n=27; median survival=52 months) was significantly longer than that of patients with a high fold-change of up-regulated miR-196a (n=21; median survival=46 months) (p=0.003). Hence, miR-193b and miR-196a may be applied as novel and promising prognostic markers in gastric cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2329-2334
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• 2012

Introduction: Many studies have reported that microRNA-21 (miR-21) mihght predict the survival outcome in non-small cell lung cancers (NSCLCs) but the opposite opinion has also been expressed. The aim of this study was to summarize the evidence for a prognostic role of miR-21. Materials and Methods: All the eligible studies was searched by Medline and EMBASE and patients' clinical characteristics and survival outcome were extracted. Then a meta-analysis was performed to clarify the prognostic role of the miR-21 expression in different subgroups. Results: A total of 8 eligible articles were yielded covering survival outcomes or clinical characteristics. The combined hazard ratio (HR) and 95% confidence interval (95% CI) for overall survival (OS) was 2.19 [0.76, 6.30], while the combined HR (95% CI) of Asian group for OS had a significant result, 5.49 [2.46, 12.27]. The combined HR (95% CI) for recurrence free survival or disease free survival (RFS/DFS) was 2.31 [1.52, 3.49]. Odds ratios (ORs) showed that the miR-21 expression was associated with lymph node status and histological type. Conclusion: miR-21 expression could predict the prognostic outcome of NSCLC in Asians, despite some deficiencies in the study data.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1939-1944
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• 2015

MicroRNA-27a (miR-27a) is deemed to be an oncogene that plays an important role in development of various cancers, and single nucleotide polymorphism (SNP) of miR-27a can influence the maturation or aberrant expression of hsa-miR27a, resulting in increased risk of cancer and poor prognosis for non-small cell lung cancer (NSCLC). This study aimed to assess the effects of rs895819 within miR-27a on susceptibility and prognosis of NSCLC patients in 560 clinical confirmed cases and 568 healthy check-up individuals. Adjusted odds/hazard ratios (ORs/HRs) and 95% confidential intervals (CIs) were calculated to evaluate the association between rs895819 and the risk and prognosis of NSCLC. The results showed that allele A and genotype GG of rs895819 were significantly associated with an increased risk of NSCLC (38.9% vs 30.8%, adjusted OR=1.26, 95%CI=1.23-1.29 for allele G vs A; 18.1% vs 11.7%, adjusted OR=1.67, 95%CI=1.59-1.75 for genotype GG vs AA). Moreover, positive associations were also observed in dominant and recessive models (53.7% vs 49.9%, adjusted OR=1.17, 95%CI=1.13-1.20 for GG/AG vs AA; 18.1% vs 11.7%, adjusted=1.65, 95%CI=1.58-1.73). However, no significant association was found between rs895819 and the prognosis of NSCLC in genotype, dominant and recessive models. These results suggested that miR-27a might be involved in NSCLC carcinogenesis, but not in progression of NSCLC. The allele G, genotype GG and allele G carrier (GG/AG vs AA) of rs895819 might be genetic susceptible factors for NSCLC. Further multi-central, large sample size and well-designed prospective studies as well as functional studies are warranted to verify our findings.

• Genomics & Informatics
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• v.13 no.3
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• pp.70-75
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• 2015

MicroRNAs (miRNAs) have been demonstrated to play an important role in carcinogenesis. Previous studies revealed that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. In this study, we measured the plasma expression levels of three miRNAs (miR-21, miR-27a, and miR-155) to investigate the usefulness of miRNAs for gastric cancer detection. We initially examined plasma miRNA expression levels in a screening cohort consisting of 15 patients with gastric cancer and 15 healthy controls from Korean population, using TaqMan quantitative real-time polymerase chain reaction. We observed that the expression level of miR-27a was significantly higher in patients with gastric cancer than in healthy controls, whereas the miR-21 and miR-155a expression levels were not significantly higher in the patients with gastric cancer. Therefore, we further validated the miR-27a expression level in 73 paired gastric cancer tissues and in a validation plasma cohort from 35 patients with gastric cancer and 35 healthy controls. In both the gastric cancer tissues and the validation plasma cohort, the miR-27a expression levels were significantly higher in patients with gastric cancer. Receiver-operator characteristic (ROC) analysis of the validation cohort, revealed an area under the ROC curve value of 0.70 with 75% sensitivity and 56% specificity in discriminating gastric cancer. Thus, the miR-27a expression level in plasma could be a useful biomarker for the diagnosis and/or prognosis of gastric cancer.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.73.1-73.16
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• 2023

Background: Highly pathogenic avian influenza virus (HPAIV) is considered a global threat to both human health and the poultry industry. MicroRNAs (miRNA) can modulate the immune system by affecting gene expression patterns in HPAIV-infected chickens. Objectives: To gain further insights into the role of miRNAs in immune responses against H5N1 infection, as well as the development of strategies for breeding disease-resistant chickens, we characterized miRNA expression patterns in tracheal tissues from H5N1-infected Ri chickens. Methods: miRNAs expression was analyzed from two H5N1-infected Ri chicken lines using small RNA sequencing. The target genes of differentially expressed (DE) miRNAs were predicted using miRDB. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were then conducted. Furthermore, using quantitative real-time polymerase chain reaction, we validated the expression levels of DE miRNAs (miR-22-3p, miR-146b-3p, miR27b-3p, miR-128-3p, miR-2188-5p, miR-451, miR-205a, miR-203a, miR-21-3p, and miR-200a3p) from all comparisons and their immune-related target genes. Results: A total of 53 miRNAs were significantly expressed in the infection samples of the resistant compared to the susceptible line. Network analyses between the DE miRNAs and target genes revealed that DE miRNAs may regulate the expression of target genes involved in the transforming growth factor-beta, mitogen-activated protein kinase, and Toll-like receptor signaling pathways, all of which are related to influenza A virus progression. Conclusions: Collectively, our results provided novel insights into the miRNA expression patterns of tracheal tissues from H5N1-infected Ri chickens. More importantly, our findings offer insights into the relationship between miRNA and immune-related target genes and the role of miRNA in HPAIV infections in chickens.

• Journal of Oral Medicine and Pain
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• v.44 no.1
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• pp.25-30
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• 2019

Purpose: The exact causes of burning mouth syndrome (BMS) is unclear so far. There are many studies to elucidate the relation between oral disease and genetic predisposition. In this study, we first tried to investigate salivary exosomal genetic components that could play an important role for diagnosing and elucidating the progression of BMS. Methods: We compared salivary exosomal micro RNAs (miRNAs) of BMS Patients to those of control using next generation sequencing (NGS). Unstimulated whole saliva from 15 patients with BMS and 10 control subjects were divided into two sets. Isolated exosomes and their total RNAs were subject to NGS for the screening of miRNAs. Results: There were up-regulated 10 exosomal miRNAs (hsa-miR-1273h-5p, hsa-miR-1273a, hsa-miR-1304-3p, hsa-miR-4449, hsa-miR-1285-3p, hsa-miR-6802-5p, hsa-miR-1268a, hsa-miR-1273d, hsa-miR-1273f, and hsa-miR-423-5p) and down-regulated 18 exosomal miRNAs (hsa-miR-27b-3p, hsa-miR-16-5p, hsa-miR-186-5p, hsa-miR-142-3p, hsa-miR-141-3p, hsa-miR-150-5p, hsa-miR-374a-5p, hsa-miR-93-5p, hsa-miR-29c-3p, hsa-miR-29a-3p, hsa-miR-148a-3p, hsa-miR-22-3p, hsa-miR-27a-3p, hsa-miR-424-5p, hsa-miR-19b-3p, hsa-miR-99a-5p, hsa-miR-548d-3p, and hsa-miR-19a-3p) in BMS patients comparing with those of control subjects. Conclusions: We show that there are 28 differential expression of miRNAs between the patients with BMS and those of control subjects. The specific function of indicated miRNAs should be further elucidated.

• Clinical and Experimental Reproductive Medicine
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• v.36 no.4
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• pp.265-274
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• 2009

Objective: MicroRNAs (miR) are known to repress target genes at post-transcriptional level and play important roles in development and maturation of cell. However, the expression profiles of miR during ovarian follicle maturation have not been fully elucidated. Here, we designed this study to investigate the expression profiles of miR in oocytes and granulose cells (G-cells) after in vitro culture according to gonadotropins and adding hCG. Methods: Ovaries from 12-day-old mice (C57BL6) were removed and preantral follicles were isolated and cultured in $20\;{\mu}L$-drop of culture media with supplementation of either rFSH, rLH, or rFSH+rLH. After their full maturation, follicles were incubated with rhCG and rEGF. RNA was isolated from oocytes and G-cells, and real-time PCR were performed with primers of miR known to be expressed in the mouse ovary (mmu-miR-16, -miR-27a, -miR-126, -miR-721). Results: FSH+LH group showed the highest ovulation and MII rates among gonadotropin groups. The profiles of miRs in oocytes and G-cells differed according to gonadotropin groups and adding hCG. The profiles of miRs showed divergent changes between oocytes and G-cells. Conclusion: miR expression profiles are altered by gonadotropins and supplementation of hCG during in vitro maturation of murine follicles. Target gene study must be necessary to validate these findings.

• Molecules and Cells
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• v.41 no.9
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• pp.868-880
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• 2018

Pancreatic cancer (PC) is one of the most aggressive cancers presenting with high rates of invasion and metastasis, and unfavorable prognoses. The current study aims to investigate whether EZH2/miR-139-5p axis affects epithelial-mesenchymal transition (EMT) and lymph node metastasis (LNM) in PC, and the mechanism how EZH2 regulates miR-139-5p. Human PC and adjacent normal tissues were collected to determine expression of EZH2 and miR-139-5p, and their relationship with clinicopathological features of PC. Human PC cell line was selected, and treated with miR-139-5p mimics/inhibitors, EZH2 vector or shEZH2 in order to validate the regulation of EZH2-mediated miR-139-5p in PC cells. Dual-luciferase report gene assay and chromatin immunoprecipitation assay were employed to identify the relationship between miR-139-5p and EZH2. RT-qPCR and Western blot analysis were conducted to determine the expression of miR-139-5p, EZH2 and EMT-related markers and ZEB1/2. Tumor formation ability and in vitro cell activity were also analyzed. Highly-expressed EZH2 and poorly-expressed miR-139-5p were detected in PC tissues, and miR-139-5p and EZH2 expressions were associated with patients at Stage III/IV, with LNM and highly-differentiated tumors. EZH2 suppressed the expression of miR-139-5p through up-regulating Histone 3 Lysine 27 Trimethylation (H3K27me3). EMT, cell proliferation, migration and invasion were impeded, and tumor formation and LNM were reduced in PC cells transfected with miR-139-5p mimics and shEZH2. MiR-139-5p transcription is inhibited by EZH2 through up-regulating H3K27me3, thereby down-regulation of EZH2 and up-regulation of miR-139-5p impede EMT and LNM in PC. In addition, the EZH2/miR-139-5p axis presents as a promising therapeutic strategy for the treatment of PC.

• Biomolecules & Therapeutics
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• v.27 no.4
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• pp.414-422
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• 2019

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.