• Molecules and Cells
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• v.43 no.8
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• pp.718-727
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• 2020

The imbalance between the proliferation and apoptosis of B-cell precursors is an important contributor to the pathogenesis of B-cell precursor acute lymphoblastic leukemia (BCP-ALL), while its specific regulatory mechanism remains perplexing. This study aimed to expound the underlying mechanism of the proliferation and apoptosis of BCP-ALL cells from the perspective of non-coding RNA. In this study, long non-coding RNA colorectal neoplasia differentially expressed (LncRNA CRNDE) was upregulated in the bone marrow of BCP-ALL patients and BCP-ALL cell lines (NALM-6 and RS4;11). Functionally, LncRNA CRNDE knockdown restrained cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. The subsequent investigation confirmed that LncRNA CRNDE bound to miR-345-5p and negatively regulated miR-345-5p expression. The overexpression of miR-345-5p suppressed cell proliferation and boosted cell apoptosis in NALM-6 and RS4;11 cells. Further experiments revealed that miR-345-5p downregulated cyclic AMP response element-binding protein (CREB) expression by targeting its mRNA directly. CREB overexpression reversed the effect of miR-345-5p mimic on cell proliferation and apoptosis in NALM-6 and RS4;11 cells. Finally, in vivo experiments showed that LncRNA CRNDE knockdown prolonged the survival of mice xenotransplanted with NALM-6 cells. In conclusion, LncRNA CRNDE upregulated CREB expression by suppressing miR-345-5p, thus promoting cell proliferation and reducing cell apoptosis in BCP-ALL.

• Animal Bioscience
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• v.35 no.6
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• pp.814-825
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• 2022

Objective: This study was conducted to identify the functional long non-coding RNAs (lncRNAs) for swine lactation by RNA-seq data of mammary gland. Methods: According to the RNA-seq data of swine mammary gland, we screened lncRNAs, performed differential expression analysis, and confirmed the functional lncRNAs for swine lactation by validation of genome wide association study (GWAS) signals, functional annotation and weighted gene co-expression network analysis (WGCNA). Results: We totally identified 286 differentially expressed (DE) lncRNAs in mammary gland at different stages from 14 days prior to (-) parturition to day 1 after (+) parturition, and the expressions of most of lncRNAs were strongly changed from day -2 to day +1. Further, the GWAS signals of sow milk ability trait were significantly enriched in DE lncRNAs. Functional annotation revealed that these DE lncRNAs were mainly involved in mammary gland and lactation developing, milk composition metabolism and colostrum function. By performing weighted WGCNA, we identified 7 out of 12 lncRNA-mRNA modules that were highly associated with the mammary gland at day -14, day -2, and day +1, in which, 35 lncRNAs and 319 mRNAs were involved. Conclusion: This study suggested that 18 lncRNAs and their 20 target genes were promising candidates for swine parturition and colostrum occurrence processes. Our research provided new insights into lncRNA profiles and their regulating mechanisms from colostrogenesis to lactogenesis in swine.

• 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.

• Journal of Microbiology and Biotechnology
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• v.31 no.10
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• pp.1331-1342
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• 2021

In this study, we evaluated the mechanism of long non-coding RNA MIR22 host gene (LncRNA MIR22HG) in osteosarcoma cells. Forty-eight paired osteosarcoma and adjacent tissues samples were collected and the bioinformatic analyses were performed. Target genes and potential binding sites of MIR22HG, microRNA (miR)-629-5p and tet methylcytosine dioxygenase 3 (TET3) were predicted by Starbase and TargetScan V7.2 and confirmed by dual-luciferase reporter assay. Cell Counting Kit-8, colony formation and flow cytometry assays were utilized to determine the viability, proliferation and apoptosis of transfected osteosarcoma cells. Pearson's analysis was introduced for the correlation analysis between MIR22HG and miR-629-5p in osteosarcoma tissue. Relative expressions of MIR22HG, miR-629-5p and TET3 were measured by quantitative real-time polymerase chain reaction or Western blot. MiR-629-5p could competitively bind with and was negatively correlated with MIR22HG, the latter of which was evidenced by the high expression of miR-629-5p and low expression of MIR22HG in osteosarcoma tissues. Overexpressed MIR22HG repressed the viability and proliferation but enhanced apoptosis of osteosarcoma cells, which was reversed by miR-629-5p upregulation. TET3 was the target gene of miR-629-5p, and the promotive effects of upregulated miR-629-5p on the viability and proliferation as well as its repressive effect on apoptosis were abrogated via overexpressed TET3. To sum up, overexpressed MIR22HG inhibits the viability and proliferation of osteosarcoma cells, which was achieved via regulation of the miR-629-5p/TET3 axis.

• BMB Reports
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• v.55 no.6
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• pp.281-286
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• 2022

Hepatocellular carcinoma is a major health burden, and though various treatments through much research are available, difficulties in early diagnosis and drug resistance to chemotherapy-based treatments render several ineffective. Cancer stem cell model has been used to explain formation of heterogeneous cell population within tumor mass, which is one of the underlying causes of high recurrence rate and acquired chemoresistance, highlighting the importance of CSC identification and understanding the molecular mechanisms of CSC drivers. Extracellular CSC-markers such as CD133, CD90 and EpCAM have been used successfully in CSC isolation, but studies have indicated that increasingly complex combinations are required for accurate identification. Pseudogene-derived long non-coding RNAs are useful candidates as intracellular CSC markers - factors that regulate pluripotency and self-renewal - given their cancer-specific expression and versatile regulation across several levels. Here, we present the use of microarray data to identify stemness-associated factors in liver cancer, and selection of sole pseudogene-derived lncRNA ZNF204P for experimental validation. ZNF204P knockdown impairs cell proliferation and migration/invasion. As the cytosolic ZNF204P shares miRNA binding sites with OCT4 and SOX2, well-known drivers of pluripotency and self-renewal, we propose that ZNF204P promotes tumorigenesis through the miRNA-145-5p/OCT4, SOX2 axis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.2971-2977
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• 2014

Background: Long non-coding RNAs (lncRNAs) have been recently observed in various human cancers. However, the role of lncRNAs in pancreatic duct adenocarcinoma (PDAC) remains unclarified. The aim of this study was to detect the expression of lncRNA MALAT1 in PDAC formalin-fixed, paraffin embedded (FFPE) tissues and to investigate the clinical significance of the MALAT1 level. Methods: The expression of MALAT1 was examined in 45 PDAC and 25 adjacent non-cancerous FFPE tissues, as well as in five PDAC cell lines and a normal pancreatic epithelium cell line HPDE6c-7, using qRT-PCR. The relationship between MALAT1 level and clinicopathological parameters of PDAC was analyzed with the Kaplan-Meier method and Cox proportional hazards model. Results: The relative level of MALAT1 was significantly higher in PDAC compared to the adjacent normal pancreatic tissues (p=0.009). When comparing the MALAT1 level in the cultured cell lines, remarkably higher expression of MALAT1 was found in aspc-1 PDAC cells compared with the immortal pancreatic duct epithelial cell line HPDE6c-7 (q=7.573, p<0.05). Furthermore, MALAT1 expression level showed significant correlation with tumor size (r=0.35, p=0.018), tumor stage (r=0.439, p=0.003) and depth of invasion (r=0.334, p=0.025). Kaplan-Meier analysis revealed that patients with higher MALAT1 expression had a poorer disease free survival (p=0.043). Additionally, multivariate analysis indicated that overexpression of MALAT1, as well as the tumor location and nerve invasion, was an independent predictor of disease-specific survival of PDAC. Conclusion: MALAT1 might be considered as a potential prognostic indicator and may be a target for diagnosis and gene therapy for PDAC.

• Genomics & Informatics
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• v.16 no.4
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• pp.25.1-25.5
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• 2018

Coronary artery disease (CAD) is one of the leading causes of death and disability all around the world. Recent studies have revealed that aberrantly regulated long non-coding RNA (lncRNA) as one of the main classes of cellular transcript plays a key regulatory role in transcriptional and epigenetic pathways. Recent reports have demonstrated that circulating lncRNAs in the blood can be potential biomarkers for CAD. HOTAIR is one of the most cited lncRNAs with a critical role in the initiation and progression of the gene expression regulation. Recent research on the role of the HOTAIR in cardiovascular disease lays the basis for the development of new studies considering this lncRNA as a potential biomarker and therapeutic target in CAD. In this study, we aimed to compare the expression of HOTAIR lncRNA in the blood samples of patients with CAD and control samples. The expression level was examined by semi-quantitative reverse transcriptase polymerase chain reaction technique. Our data shows that expression of HOTAIR is up-regulated in blood samples of patients with CAD.

• International Journal of Industrial Entomology and Biomaterials
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• v.46 no.2
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• pp.41-54
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• 2023

The blue-tailed damselfly, Ischnura elegans Van der Linden, 1820 (Odonata: Coenagrionidae), is a climate-sensitive indicator species in South Korea. In this study, we sequenced the complete mitochondrial genome (mitogenome) of I. elegans collected from South Korea for subsequent population genetic analysis, particularly to trace population movements in response to climate change. The 15,963 base pair (bp)-long complete mitogenome of I. elegans has typical sets of genes including a major non-coding region (the A+T-rich region), and an arrangement identical to that observed in ancestral insect species. The ATP6, ND3 and ND1 genes have the TTG start codon, which, although rare, is the canonical start codon for animal mitochondrial tRNA. The A/T content was 71.4% in protein-coding genes, 72.1% in tRNAs, 72.9% in the whole genome, 74.7% in srRNA, 75.3% in lrRNA, and 83.8% in the A+T-rich region. The A+T-rich region is unusually long (1,196 bp) and contains two subunits (192 bp and 176-165 bp), each of which is tandemly triplicated and surrounded by non-repeat sequences. Comparison of the sequence divergence among available mitogenomes of I. elegans, including the one from the current study, revealed ND2 as the most variable gene, followed by COII and COI, suggesting that ND2 should be targeted first in subsequent population-level studies. Phylogenetic reconstruction based on all available mitogenome sequences of Coenagrionidae showed a strong sister relationship between I. elegans and I. senegalensis.

• Clinical and Experimental Reproductive Medicine
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• v.49 no.4
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• pp.225-238
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• 2022

The ultimate goal of human assisted reproductive technology is to achieve a healthy pregnancy and birth, ideally from the selection and transfer of a single competent embryo. Recently, techniques for efficiently evaluating the state and quality of preimplantation embryos using time-lapse imaging systems have been applied. Artificial intelligence programs based on deep learning technology and big data analysis of time-lapse monitoring system during in vitro culture of preimplantation embryos have also been rapidly developed. In addition, several molecular markers of the secretome have been successfully analyzed in spent embryo culture media, which could easily be obtained during in vitro embryo culture. It is also possible to analyze small amounts of cell-free nucleic acids, mitochondrial nucleic acids, miRNA, and long non-coding RNA derived from embryos using real-time polymerase chain reaction (PCR) or digital PCR, as well as next-generation sequencing. Various efforts are being made to use non-invasive evaluation of embryo quality (NiEEQ) to select the embryo with the best developmental competence. However, each NiEEQ method has some limitations that should be evaluated case by case. Therefore, an integrated analysis strategy fusing several NiEEQ methods should be urgently developed and confirmed by proper clinical trials.

• Molecules and Cells
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• v.28 no.4
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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.