• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1851-1855
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• 2015

Background: There are increasing data about microRNAs (miRNA) in the literature, providing abundant evidence that they play important roles in pathogenesis and development of colorectal cancer. In this study, we aimed to investigate the miRNA expression profiles in surgically resected specimens of patients with recurrent and non-recurrent colorectal cancer. Materials and Methods: The study population included 40 patients with stage II colorectal cancer (20 patients with recurrent tumors, and 20 sex and age matched patients without recurrence), who underwent curative colectomy between 2004 and 2011 without adjuvant therapy. Expression of 16 miRNAs (miRNA-9, 21, 30d, 31, 106a, 127, 133a, 133b, 135b, 143, 145, 155, 182, 200a, 200c, 362) was verified by quantitative real-time polymerase chain reaction (qRT-PCR) in all resected colon cancer tissue samples and in corresponding normal colonic tissues. Data analyses were carried out using SPSS 15 software. Values were statistically significantly changed in 40 cancer tissues when compared to the corresponding 40 normal colonic tissues (p<0.001). MiR-30d, miR-133a, miR-143, miR-145 and miR-362 expression was statistically significantly downregulated in 40 resected colorectal cancer tissue samples (p<0.001). When we compared subgroups, miRNA expression profiles of 20 recurrent cancer tissues were similar to all 40 cancer tissues. However in 20 non-recurrent cancer tissues, miR-133a expression was not significantly downregulated, moreover miR-133b expression was significantly upregulated (p<0.05). Conclusions: Our study revealed dysregulation of expression of ten miRNAs in Turkish colon cancer patients. These miRNAs may be used as potential biomarkers for early detection, screening and surveillance of colorectal cancer, with functional effects on tumor cell behavior.

• Journal of Veterinary Science
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• 제21권6호
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• pp.81.1-81.10
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• 2020

Background: Although previous in vivo studies explored urinary microRNA (miRNA), there is no agreement on nephrotoxicity-specific miRNA biomarkers. Objectives: In this study, we assessed whether urinary miRNAs could be employed as biomarkers for nephrotoxicity. Methods: For this, literature-based candidate miRNAs were identified by reviewing the previous studies. Female Sprague-Dawley rats received subcutaneous injections of a single dose or repeated doses (3 consecutive days) of gentamicin (GEN; 137 or 412 mg/kg). The expression of miRNAs was analyzed by real-time reverse transcription-polymerase chain reaction in 16 h pooled urine from GEN-treated rats. Results: GEN-induced acute kidney injury was confirmed by the presence of tubular necrosis. We identified let-7g-5p, miR-21-3p, 26b-3p, 192-5p, and 378a-3p significantly upregulated in the urine of GEN-treated rats with the appearance of the necrosis in proximal tubules. Specifically, miR-26-3p, 192-5p, and 378a-3p with highly expressed levels in urine of rats with GEN-induced acute tubular injury were considered to have sensitivities comparable to clinical biomarkers, such as blood urea nitrogen, serum creatinine, and urinary kidney injury molecule protein. Conclusions: These results indicated the potential involvement of urinary miRNAs in chemical-induced nephrotoxicity, suggesting that certain miRNAs could serve as biomarkers for acute nephrotoxicity.

• Nutrition Research and Practice
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• 제14권4호
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• pp.412-422
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• 2020

BACKGROUND/OBJECTIVES: This study investigates correlations between circulating microRNAs (miRNAs) and obesity-related parameters among young women (aged 20-30 years old) in Korea. SUBJECTS/METHODS: We analyzed TaqMan low density arrays (TLDAs) of circulating miRNAs in 9 lean (body mass index [BMI] < 25 kg/㎡) and 15 obese (BMI > 25 kg/㎡) women. We also performed gene ontology (GO) analyses of the biological functions of predicted miRNA target genes, and clustered the results using the database for annotation, visualization and integrated discovery. RESULTS: The TLDA cards contain 754 human miRNAs; of these, the levels of 8 circulating miRNAs significantly declined (> 2-fold) in obese subjects compared with those in lean subjects, including miR-1227, miR-144-5p, miR-192, miR-320, miR-320b, miR-484, miR-324-3p, and miR-378. Among them, miR-484 and miR-378 displayed the most significant inverse correlations with BMI (miR-484, r = -0.5484, P = 0.0056; miR-378, r = -0.5538, P = 0.0050) and visceral fat content (miR-484, r = -0.6141, P = 0.0014; miR-378, r = -0.6090, P = 0.0017). GO analysis indicated that genes targeted by miR-484 and miR-378 had major roles in carbohydrate and lipid metabolism. CONCLUSION: Our result showed the differentially expressed circulating miRNAs in obese subjects compared to lean subjects. Although the mechanistic study to reveal the causal role of miRNAs remains, these miRNAs may be novel biomarkers for obesity.

• Tuberculosis and Respiratory Diseases
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• 제67권5호
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• pp.413-421
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• 2009

Background: MicroRNAs (miRNAs) play an important role in the regulation of cell proliferation, apoptosis, development and differentiation. Several studies have shown that aberrant expression of miRNAs is involved in cancer development and progression by regulating the expression of proto-oncogenes or tumor suppressor genes. In this study, we investigated miRNA expression profiles in Korean patients with non-small cell lung cancer (NSCLC). Methods: We performed miRNA microarray analysis containing 60~65 bp oligonucleotide probes representing human 318 miRNAs and validated the results of the microarray with Northern blot analysis or quantitative RT-PCR. Next, we examined the correlation between miRNA expression and the target gene transcriptional profile using a human whole-genome-expression microarray. Results: We showed that 35 miRNAs were expressed differentially in the NSCLCs and corresponding non-malignant lung tissues. We showed that 35 miRNAs were expressed differentially in the NSCLCs and corresponding nonmalignant lung tissues. Thirteen of the 35 differentially expressed miRNAs were newly identified in the present study. Of the 35 miRNAs, 2 (miR-371 and miR-210) were over-expressed in lung cancers, and 33 miRNAs, including miR-145, were under-expressed in lung cancers. miR-99b expression consistently showed a negative correlation with FGFR3 expression. Conclusion: Albeit a small number of patients were examined, these results suggest that miRNA expression profiles in Korean lung cancers may be somewhat different from the expression profiles reported on lung cancers in Western populations. The findings suggest that miR-99b might be a tumor suppressor through its up-regulation of FGFR3.

• 한국어병학회지
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• 제33권1호
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• pp.35-43
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• 2020

Hypoxia is a serious problem in the marine ecosystem causing a decline in aquatic resources. MicroRNAs (miRNAs) regulate the expression of genes through binding to the corresponding sequences of their target mRNAs. Especially, miRNAs in the cytoplasm can be secreted into body fluids, which called circulating miRNAs, and the availability of circulating miRNAs as biomarkers for hypoxia has been demonstrated in mammals. However, there has been no report on the hypoxia-mediated changes in the circulating miRNAs in fish. miR-210 is known as the representative hypoxia-responsive circulating miRNA in mammals. To know whether fish miR-210 also respond to hypoxia, we analyzed the change of circulating miR-210 quantity in the serum of olive flounder (Paralichthys olivaceus) in response to hypoxia. The expression of hypoxia related genes, hypoxia inducible factor 1α (HIF-1α) and the heat shock protein 90α (HSP90α) was also analyzed. Similar to the reports from mammals, miR-210-5p and miR-210-3p were significantly increased in the serum of olive flounder in response to hypoxia, suggesting that circulating miR-210 levels in the serum can be used as a noninvasive prognostic biomarker for fish suffered hypoxia. The target genes of miR-210 were related to various biological processes, which explains the major regulatory role of miR-210 in response to hypoxia. The expression of HIF-1α and HSP90α in the tissues was also up-regulated by hypoxia. Considering the critical role of HIF-1α in miR-210 expression and HSP90 in miRNAs function, the present up-regulation of HIF-1α and HSP90α might be related to the increase of circulatory miR-210, and the interaction mechanism among HIF-1α, HSP90α, and hypoxia-responsive microRNAs in fish should be further studied.

• Molecules and Cells
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• 제28권4호
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• pp.341-345
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• 2009

MiRNAs are non-coding RNAs that play a role in the regulation of major processes. The inhibition of miRNAs using antisense oligonucleotides (ASOs) is a unique and effective technique for the characterization and subsequent therapeutic targeting of miRNA function. Recent advances in ASO chemistry have been used to increase both the resistance to nucleases and the target affinity and specificity of these ASOs. Peptide nucleic acids (PNAs) are artificial oligonucleotides constructed on a peptide-like backbone. PNAs have a stronger affinity and greater specificity to DNA or RNA than natural nucleic acids and are resistant to nucleases, which is an essential characteristic for a miRNA inhibitor that will be exposed to serum and cellular nucleases. For increasing cell penetration, PNAs were conjugated with cell penetrating peptides (CPPs) at N-terminal. Among the tested CPPs, Tat-modified peptide-conjugated PNAs have most effective function for miRNA inhibition. PNA-based ASO was more effective miRNA inhibitor than other DNA-based ASOs and did not show cytotoxicity at concentration up to 1,000 nM. The effects of PNA-based ASOs were shown to persist for 9 days. Also, PNA-based ASOs showed considerable stability at storage temperature. These results suggest that PNA-based ASOs are more effective ASOs of miRNA than DNA-based ASOs and PNA-based ASO technology, compared with other technologies used to inhibit miRNA activity can be an effective tool for investigating miRNA functions.

• Journal of Ginseng Research
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• 제40권2호
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• pp.151-159
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• 2016

Background: Ginsenoside-Rg3, the pharmacologically active component of red ginseng, has been found to inhibit tumor growth, invasion, metastasis, and angiogenesis in various cancer models. Previously, we found that 20(R)-ginsenoside-Rg3 (Rg3) could inhibit angiogenesis. Since microRNAs (miRNAs) have been shown to affect many biological processes, they might play an important role in ginsenoside-mediated angiomodulation. Methods: In this study, we examined the underlying mechanisms of Rg3-induced angiosuppression through modulating the miRNA expression. In the miRNA-expression profiling analysis, six miRNAs and three miRNAs were found to be up- or down-regulated in vascular-endothelial-growth-factor-induced human-umbilical-vein endothelial cells (HUVECs) after Rg3 treatment, respectively. Results: A computational prediction suggested that mature hsa-miR-520h (miR-520h) targets ephrin receptor (Eph) B2 and EphB4, and hence, affecting angiogenesis. The up-regulation of miR-520h after Rg3 treatment was validated by quantitative real-time polymerase chain reaction, while the protein expressions of EphB2 and EphB4 were found to decrease, respectively. The mimics and inhibitors of miR- 520h were transfected into HUVECs and injected into zebra-fish embryos. The results showed that overexpression of miR-520h could significantly suppress the EphB2 and EphB4 protein expression, proliferation, and tubulogenesis of HUVECs, and the subintestinal-vessel formation of the zebra fish. Conclusion: These results might provide further information on the mechanism of Rg3-induced angiosuppression and the involvement of miRNAs in angiogenesis.

• Asian-Australasian Journal of Animal Sciences
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• 제29권6호
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• pp.782-792
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• 2016

As the most common neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD) are two of the main health concerns for the elderly population. Recently, microRNAs (miRNAs) have been used as biomarkers of infectious, genetic, and metabolic diseases in humans but they have not been well studied in domestic animals. Here we describe a computational biology study in which human AD- and PD-associated miRNAs (ADM and PDM) were utilized to predict orthologous miRNAs in the following domestic animal species: dog, cow, pig, horse, and chicken. In this study, a total of 121 and 70 published human ADM and PDM were identified, respectively. Thirty-seven miRNAs were co-regulated in AD and PD. We identified a total of 105 unrepeated human ADM and PDM that had at least one 100% identical animal homolog, among which 81 and 54 showed 100% sequence identity with 241 and 161 domestic animal miRNAs, respectively. Over 20% of the total mature horse miRNAs (92) showed perfect matches to AD/PD-associated miRNAs. Pigs, dogs, and cows have similar numbers of AD/PD-associated miRNAs (63, 62, and 59). Chickens had the least number of perfect matches (34). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that humans and dogs are relatively similar in the functional pathways of the five selected highly conserved miRNAs. Taken together, our study provides the first evidence for better understanding the miRNA-AD/PD associations in domestic animals, and provides guidance to generate domestic animal models of AD/PD to replace the current rodent models.

• 생명과학회지
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• 제30권9호
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• pp.772-782
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• 2020

골격근의 분화 또는 근육 분화는 근육량과 신진대사 항상성을 유지하기 위해 중요하다. 근육 특이적 microRNAs (miRNAs)는 골격근 분화에 중요한 역할을 한다. 본 연구에서는 rat miRNAs 마이크로어레이를 사용하여 rat L6 근아세포의 근육 분화 과정에서의 miRNAs 발현 양상을 조사했다. 우리는 miR-128의 발현 증가를 발견했고, 동시에 이미 알려진 근육 분화 조절 miRNAs인 miR-1, miR-133b와 mi-206의 발현 증가를 확인했다. 이 microarray 결과를 확인하기위해 우리는 Quantitative RT-PCR 기술을 사용하였고, microarray 결과와 유사하게 발현 초기 mRNAs와 발현 후 성숙 miRNAs에서 모두 miR-128의 발현 증가를 확인했다. 또한 Rat L6 근아세포로의 miR-128 발현 향상은 muscle creatine kinase (MCK), myogenin, myosin heavy chain (MHC)와 같은 근육분화 표지 유전자 발현을 유발했고, 또한 MHC의 단백질 발현을 증가시켰다. 억제 PNAs를 사용한 miR-128의 작용 억제는 이러한 근육 분화 표지 유전자들의 발현을 차단했다. 또한, miR-128 발현 향상은 Erk와 Akt 단백질의 인슐린 자극에 의한 인산화를 증가시켰고, 고인슐린혈증과 고혈당증으로 인해 유도된 인슐린 저항성으로 인한 Erk와 Akt의 억제된 인산화를 회복했다. 이러한 발견은 miR-128이 근육분화와 인슐린 작용에 중요한 역할을 할 수 있다는 것을 시사한다.

• Genomics & Informatics
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• 제21권3호
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• pp.38.1-38.8
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• 2023

Non-small cell lung cancer (NSCLC) is an important cause of cancer-associated deaths worldwide. Therefore, the exact molecular mechanisms of NSCLC are unidentified. The present investigation aims to identify the miRNAs with predictive value in NSCLC. The two datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEmiRNA) and mRNAs (DEmRNA) were selected from the normalized data. Next, miRNA-mRNA interactions were determined. Then, co-expression network analysis was completed using the WGCNA package in R software. The co-expression network between DEmiRNAs and DEmRNAs was calculated to prioritize the miRNAs. Next, the enrichment analysis was performed for DEmiRNA and DEmRNA. Finally, the drug-gene interaction network was constructed by importing the gene list to dgidb database. A total of 3,033 differentially expressed genes and 58 DEmiRNA were recognized from two datasets. The co-expression network analysis was utilized to build a gene co- expression network. Next, four modules were selected based on the Z_summary score. In the next step, a bipartite miRNA-gene network was constructed and hub miRNAs (let-7a-2-3p, let-7d-5p, let-7b-5p, let-7a-5p, and let-7b-3p) were selected. Finally, a drug-gene network was constructed while SUNITINIB, MEDROXYPROGESTERONE ACETATE, DOFETILIDE, HALOPERIDOL, and CALCITRIOL drugs were recognized as a beneficial drug in NSCLC. The hub miRNAs and repurposed drugs may act a vital role in NSCLC progression and treatment, respectively; however, these results must validate in further clinical and experimental assessments.