• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.233-239
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• 2024

N6-methyladenosine (m6A) RNA methylation has recently emerged as a significant co-transcriptional modification involved in regulating various RNA functions. It plays a vital function in numerous biological processes. Enzymes referred to as m6A methyltransferases, such as the methyltransferase-like (METTL) 3-METTL14-Wilms tumor 1 (WT1)-associated protein (WTAP) complex, are responsible for adding m6A modifications, while m6A demethylases, including fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5), can remove m6A methylation. The functions of m6A-methylated RNA are regulated through the recognition and interaction of m6A reader proteins. Recent research has shown that m6A methylation takes place at multiple sites within hepatitis B virus (HBV) RNAs, and the location of these modifications can differentially impact the HBV infection. The addition of m6A modifications to HBV RNA can influence its stability and translation, thereby affecting viral replication and pathogenesis. Furthermore, HBV infection can also alter the m6A modification pattern of host RNA, indicating the virus's ability to manipulate host cellular processes, including m6A modification. This manipulation aids in establishing chronic infection, promoting liver disease, and contributing to pathogenesis. A comprehensive understanding of the functional roles of m6A modification during HBV infection is crucial for developing innovative approaches to combat HBV-mediated liver disease. In this review, we explore the functions of m6A modification in HBV replication and its impact on the development of liver disease.

• BMB Reports
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• v.28 no.1
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• pp.27-32
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• 1995

Polyclonal antibodies against human DNA-dependent RNA polymerase II (HPP II) were generated from chicken egg yolk after immunization with RNA polymerase II as an antigen. The antibodies from egg yolk (IgY) were purified and characterized. IgY showed a specificity against DNA-dependent RNA polymerase II, and was a polyclonal antibody against 12 subunits of polymerase II. An amount of 0.35 mg of IgY was obtained freman HPP II-Sepharose affinity column using 10 eggs from a chicken immunized against RNA polymerase II as an antigen. These antibodies can be used for isolating the genes for RNA polymerase II components, and for in vitro transcription assays using HP-RNA polymerase II.

• BMB Reports
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• v.48 no.4
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• pp.234-237
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• 2015

Aptamers, composed of single-stranded DNA or RNA oligonucleotides that interact with target molecules through a specific three-dimensional structure, are selected from pools of combinatorial oligonucleotide libraries. With their high specificity and affinity for target proteins, ease of synthesis and modification, and low immunogenicity and toxicity, aptamers are considered to be attractive molecules for development as anticancer therapeutics. Two aptamers - one targeting nucleolin and a second targeting CXCL12 - are currently undergoing clinical trials for treating cancer patients, and many more are under study. In this mini-review, we present the current clinical status of aptamers and aptamer-based cancer therapeutics. We also discuss advantages, limitations, and prospects for aptamers as cancer therapeutics. [BMB Reports 2015; 48(4): 234-237]

• Journal of Cancer Prevention
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• v.22 no.4
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• pp.203-210
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• 2017

After transcription, RNAs are always associated with RNA binding proteins (RBPs) to perform biological activities. RBPs can interact with target RNAs in sequence- and structure-dependent manner through their unique RNA binding domains. In development and progression of carcinogenesis, RBPs are aberrantly dysregulated in many human cancers with various mechanisms, such as genetic alteration, epigenetic change, noncoding RNA-mediated regulation, and post-translational modifications. Upon deregulation in cancers, RBPs influence every step in the development and progression of cancer, including sustained cell proliferation, evasion of apoptosis, avoiding immune surveillance, inducing angiogenesis, and activating metastasis. To develop therapeutic strategies targeting RBPs, RNA interference-based oligonucleotides or small molecule inhibitors have been screened based on reduced RBP-RNA interaction and changed level of target RNAs. Identification of binding RNAs with high-throughput techniques and integral analysis of multiple datasets will help us develop new therapeutic drugs or prognostic biomarkers for human cancers.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2425-2430
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• 2015

Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.5
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• pp.403-411
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• 2024

The global spread of flaviviruses has triggered major outbreaks worldwide, significantly impacting public health, society, and economies. This has intensified research efforts to understand how flaviviruses interact with their hosts and manipulate the immune system, underscoring the need for advanced research tools. RNA-sequencing (RNA-seq) technologies have revolutionized our understanding of flavivirus infections by offering transcriptome analysis to dissect the intricate dynamics of virus-host interactions. Bulk RNA-seq provides a macroscopic overview of gene expression changes in virus-infected cells, offering insights into infection mechanisms and host responses at the molecular level. Single-cell RNA sequencing (scRNA-seq) provides unprecedented resolution by analyzing individual infected cells, revealing remarkable cellular heterogeneity within the host response. A particularly innovative advancement, virus-inclusive single-cell RNA sequencing (viscRNA-seq), addresses the challenges posed by non-polyadenylated flavivirus genomes, unveiling intricate details of virus-host interactions. In this review, we discuss the contributions of bulk RNA-seq, scRNA-seq, and viscRNA-seq to the field, exploring their implications in cell line experiments and studies on patients infected with various flavivirus species. Comprehensive transcriptome analyses from RNA-seq technologies are pivotal in accelerating the development of effective diagnostics and therapeutics, paving the way for innovative treatments and enhancing our preparedness for future outbreaks.

• Journal of Pharmaceutical Investigation
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• v.40 no.spc
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• pp.119-129
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• 2010

The emergence of new biological drugs based on RNA interference (RNAi) technology has been one of the most attractive issues in the field of gene therapy for years. However, the use of siRNA therapeutics in clinical settings is still limited due to lack of appropriate delivery systems for the highly charged macromolecular drug. In this review, recent development of major non-viral siRNA delivery systems, including lipid, liposome, polymer, and peptide-based carriers, is to be summarized.

• Molecules and Cells
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• v.24 no.2
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• pp.247-254
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• 2007

Improvement in the pharmacokinetic properties of short interfering RNAs (siRNAs) is a prerequisite for the therapeutic application of RNA interference technology. When injected into mice as unmodified siRNAs complexed to DOTAP/Chol-based cationic liposomes, all 12 tested siRNA duplexes caused a strong induction of cytokines including interferon ${\alpha}$, indicating that the immune activation by siRNA duplexes is independent of sequence context. When modified by various combinations of 2'-OMe, 2'-F, and phosphorothioate substitutions, introduction of as little as three 2'-OMe substitutions into the sense strand was sufficient to suppress immune activation by siRNA duplexes, whereas the same modifications were much less efficient at inhibiting the immune response of single stranded siRNAs. It is unlikely that Toll-like receptor 3 (TLR3) signaling is involved in immune stimulation by siRNA/liposome complexes since potent immune activation by ds siRNAs was induced in TLR3 knockout mice. Together, our results indicate that chemical modification of siRNA provides an effective means to avoid unwanted immune activation by therapeutic siRNAs. This improvement in the in vivo properties of siRNAs should greatly facilitate successful development of siRNA therapeutics.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.62-67
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• 2004

Trauma remains one of the important sources leading to systemic inflammatory response anti sub-sequent multiple organ failure. Although hepatic microvascular dysfunction occurs during trauma, the mechanism responsible remains unclear. The aim of this study was to investigate the effect of trauma on hepatic vascular stress gene expression. Femur fracture (EFx) was induced by torsion to the femur at midshaft. Liver samples were taken for RT-PCR analysis of mRNA for gtenes of interest: endothelin-1 (ET-1), its receptors $ET_A$ and $ET_B$, nitric oxide synthases (iNOS and eNOS), cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), and tumor necrosis tactor-${\alpha}$ (TNF-${\alpha}$). The expression of ET-1 mRNA was significantly increased by FFx. Expression of mRNA in FFx group showed no change in $ET_A$, $ET_B$, iNOS and HO-1 and showed a slight increase of 2.2-fold and 2.7-fold for eNOS tll1d COX-2, respectively. The level of TNF-${\alpha}$ mRNA significantly increased in FFx group. In conclusion, mild trauma alone causes little change in expression of vasoactive mediators.

• Journal of Yeungnam Medical Science
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• v.39 no.2
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• pp.89-97
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• 2022

More than 2 years after the explosion of the coronavirus disease 2019 (COVID-19) pandemic, extensive efforts have been made to develop safe and efficacious vaccines against infections with severe acute respiratory syndrome coronavirus 2. The pandemic has opened a new era of vaccine development based on next-generation platforms, including messenger RNA (mRNA)-based technologies, and paved the way for the future of mRNA-based therapeutics to provide protection against a wide range of infectious diseases. Multiple vaccines have been developed at an unprecedented pace to protect against COVID-19 worldwide. However, important knowledge gaps remain to be addressed, especially in terms of how vaccines induce immunogenicity and efficacy in those who are elderly. Here, we discuss the various vaccine platforms that have been utilized to combat COVID-19 and emphasize how these platforms can be a powerful tool to react quickly to future pandemics.