• The Korean Journal of Physiology and Pharmacology
• /
• 제18권5호
• /
• pp.359-363
• /
• 2014

MicroRNAs (miRs) are endogenous ${\approx}22$-nt non-coding RNAs that participate in the regulation of gene expression at post-transcriptional level. MiR-1 is one of the muscle-specific miRs, aberrant expression of miR-1 plays important roles in many physiological and pathological processes. In this review, we focus on the recent studies about miR-1 in cardiac diseases and cancers. The findings indicate that miR-1 may be a novel, important biomarker, and a potential therapeutic target in cardiac diseases and cancers.

• BMB Reports
• /
• 제42권11호
• /
• pp.725-730
• /
• 2009

Cyclin E1 (CCNE1), a positive regulator of the cell cycle, controls the transition of cells from G1 to S phase. In numerous human tumors, however, CCNE1 expression is frequently dysregulated, while the mechanism leading to its dysregulation remains incompletely defined. Herein, we showed that CCNE1 expression was subject to post-transcriptional regulation by a microRNA miR-16-1. This was evident at protein level of CCNE1 as well as its mRNA level. Further evident by dual luciferase reporter assay revealed that two evolutionary conserved binding sites on 3' UTR of CCNE1 were the direct functional target sites. Moreover, we showed that miR-16-1 induced G0/G1 cell cycle arrest by targeting CCNE1 and siRNA against CCNE1 partially phenocopied miR-16-1-induced cell cycle phenotype whereas substantially rescued anti-miR-16-1- induced phenotype. Together, all these results demonstrate that miR-16-1 plays a vital role in modulating cellular process in human cancers and indicate the therapeutic potential of miR-16-1 in cancer therapy.

• Genomics & Informatics
• /
• 제5권3호
• /
• pp.107-112
• /
• 2007

MicroRNAs (miRNAs) are known to negatively control protein-coding genes by binding to messenger RNA (mRNA) in the cytoplasm. In innate immunity, the role of miRNA gene silencing is largely unknown. In this study, we performed microarray-based experiments using lipopolysaccharide (LPS)-stimulated macrophages derived from wild-type, MyD88 knockout (KO), TRIF KO, and MyD88/TRIF double KO mice. We employed a statistical approach to determine the importance of the commonality and specificity of miRNA binding sites among groups of temporally co-regulated genes. We demonstrate that both commonality and specificity are irrelevant to define a priori groups of co-down regulated genes. In addition, analyzing the various experimental conditions, we suggest that miRNA regulation may not only be a late-phase process (after transcription) but can also occur even early (1h) after stimulation in knockout conditions. This further indicates the existence of dynamic interactions between miRNA and signaling molecules/transcription factor regulation; this is another proof for the need of shifting from a 'hard-wired' paradigm of gene regulation to a dynamical one in which the gene co-regulation is established on a case-by-case basis.

• 운동영양학회지
• /
• 제25권2호
• /
• pp.1-7
• /
• 2021

[Purpose] Recent studies have shown that COVID-19 is often associated with altered gut microbiota composition and reflects disease severity. Furthermore, various reports suggest that the interaction between COVID-19 and host-microbiota homeostasis is mediated through the modulation of microRNAs (miRNAs). Thus, in this review, we aim to summarize the association between human microbiota and miRNAs in COVID-19 pathogenesis. [Methods] We searched for the existing literature using the keywords such "COVID-19 or microbiota," "microbiota or microRNA," and "COVID-19 or probiotics" in PubMed until March 31, 2021. Subsequently, we thoroughly reviewed the articles related to microbiota and miRNAs in COVID-19 to generate a comprehensive picture depicting the association between human microbiota and microRNAs in the pathogenesis of COVID-19. [Results] There exists strong experimental evidence suggesting that the composition and diversity of human microbiota are altered in COVID-19 patients, implicating a bidirectional association between the respiratory and gastrointestinal tracts. In addition, SARS-CoV-2 encoded miRNAs and host cellular microRNAs modulated by human microbiota can interfere with viral replication and regulate host gene expression involved in the initiation and progression of COVID-19. These findings suggest that the manipulation of human microbiota with probiotics may play a significant role against SARS-CoV-2 infection by enhancing the host immune system and lowering the inflammatory status. [Conclusion] The human microbiota-miRNA axis can be used as a therapeutic approach for COVID-19. Hence, further studies are needed to investigate the exact molecular mechanisms underlying the regulation of miRNA expression in human microbiota and how these miRNA profiles mediate viral infection through host-microbe interactions.

• Nutrition Research and Practice
• /
• 제10권4호
• /
• pp.377-384
• /
• 2016

BACKGROUND/OBJECTIVES: Resveratrol, a natural polyphenol, has multiple functions in cellular responses including apoptosis, survival, and differentiation. It also participates in the regulation of inflammatory response and oxidative stress. MicroRNA-Let-7A (miR-Let7A), known as a tumor suppressor miRNA, was recently reported to play a crucial role in both inflammation and apoptosis. Therefore, we examined involvement of miR-Let7A in the modulation of inflammation and cell survival/apoptosis regulated by resveratrol. MATERIALS/METHODS: mRNA expression of pro-/anti-inflammatory cytokines and sirtuin 1 (SIRT1), and protein expression of apoptosis signal-regulating kinase 1 (ASK1), p-ASK1, and caspase-3 and cleaved caspase-3 were measured, and cell viability and Hoechst/PI staining for apoptosis were observed in Lipopolysaccharide (LPS)-stimulated human THP-1 macrophages with the treatment of resveratrol and/or miR-Let7A overexpression. RESULTS: Pre-treatment with resveratrol ($25-200{\mu}M$) resulted in significant recovery of the reduced cell viabilities under LPS-induced inflammatory condition and in markedly increased expression of miR-Let7A in non-stimulated or LPS-stimulated cells. Increased mRNA levels of tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6 induced by LPS were significantly attenuated, and decreased levels of IL-10 and brain-derived neurotrophic factor were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. Decreased expression of IL-4 mRNA by LPS stimulation was also significantly increased by miR-Let7A overexpression co-treated with resveratrol. In addition, decreased SIRT1 mRNA levels, and increased p-ASK1 levels and PI-positive cells by LPS stimulation were significantly restored by resveratrol and miR-Let7A overexpression, respectively, or in combination. CONCLUSIONS: miR-Let7A may be involved in the inflammatory response and cell survival/apoptosis modulated by resveratrol in human THP-1 macrophages.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권5호
• /
• pp.3197-3203
• /
• 2013

Background: microRNAs (miRNAs) that regulate proliferation, invasion and metastasis are considered to be the principal molecular basis of tumor heterogeneity. Breast cancer is not a homogeneous tissue. Thus, it is very important to perform microarray-based miRNA screening of tumors at different sites. Methods: Breast tissue samples from the centers and edges of tumors of 30 patients were classified into 5 clinicopathological subtypes. In each group, 6 specimens were examined by microRNA array. All differential miRNAs were analyzed between the edges and centers of the tumors. Results: Seventeen kinds of miRNAs were heterogeneously distributed in the tumors from different clinicopathological subtypes that included 1 kind of miRNA in Luminal A and Luminal B Her2+ subtypes, 4 kinds in Luminal A and Her2 overexpression subtypes, 6 kinds in Luminal B Ki67+ and Luminal B Her2+ subtypes, 2 kinds between Luminal B Ki67+ and triple-negative breast cancer (TNBC) subtypes, 2 kinds between Luminal B Her2+ and TNBC subtypes, and 2 kinds between Luminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Twenty kinds of miRNAs were homogenously distributed in the tumors from different clinicopathological subtypes that included 6 kinds of miRNAs in Luminal B Ki67+ and Luminal B Her2+ subtypes, 1 kind in Luminal B Ki67+ and Her2 overexpression subtypes, 10 kinds between Luminal B Ki67+ and TNBC subtypes, 2 kinds in Luminal B Her2+ and TNBC subtypes, and 1 kind between Luminal B Ki67+, Luminal B Her2+, and TNBC subtypes. Conclusions: A total of 37 miRNAs were significantly distributed in tumors from the centers to edges, and in all clinicopathological subtypes.

• 대한임상검사과학회지
• /
• 제47권4호
• /
• pp.298-305
• /
• 2015

최근 종양을 극복하고자 하는 새로운 접근 방법가운데 하나로, 종양세포내에 발현되는 줄기세포 전사인자들(Oct4, Sox2, KLF4 and Lin28)을 억제하여 종양을 치료하는 연구들이 증가하고 있다. 본 실험은 미분화 전사인자를 표적(조절)하는 microRNA-126을 이용하여 난소종양세포들(6종: HSC832(t)c, Ovcar3, Skov3, PA-1, TOV21G and Tov112D)들 생존과 성장에 어떠한 생물학적 변화를 유도하는지 연구하였다. Scramble과 microRNA-126를 난소종양세포들에 처리 후 세포모양 관찰결과 Skov3를 제외한 난소 종양세포들에서 형태학적 모양 변성과 부유현상을 관찰하였다. CCK-8을 이용한 세포분열능 분석에서 Skov3를 제외한 난소 종양세포들의 분열능력이 점차적으로 감소되는 것을 확인하였다. 특히 Tov112D, Tov21G and PA-1에서 각 시간대별로 뚜렷한 세포분열 능력 감소를 확인할 수 있었다. RT-PCR결과 미분화 전사인자들(Sox2, Lin28)의 발현감소를 확인할 수 있었다. 이러한 결과들은 microRNA-126이 다양한 난소 종양세포들을 표적하여 세포분열능과 사멸을 유도할 수 있는 가역적 환경(유전자 발현조절)을 제공함과 동시에 임상 치료에 대한 분자생물학적 단서를 제공할 수 있을 것이다.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 2008년도 Proceedings of the Convention
• /
• pp.23-30
• /
• 2008

Mitochondria biogenesis requires a coordination of two genomes, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Disruption of mitochondria function leads to a loss of mitochondrial membrane potential and ATP generating capacity and consequently results in chronic degenerative diseases including insulin resistance, metabolic syndrome and neurodegenerative diseases. Although PPAR-${\gamma}$ coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) was discovered as a central regulator of mitochondria biogenesis and a transcriptional co-activator of nuclear respiratory factor (NRF) and mitochondrial transcription factor A (Tfam), the expressions of PGC-$1{\alpha}$, NRF and Tfam were not significantly altered in tissues showing abnormal mitochondria functions. This observation suggests that there should be another regulator(s) for mitochondria function. Here, we demonstrate microRNAs (miRNAs) can modulate mitochondria function. Overexpression of microRNA dissipated mitochondrial membrane potential and increased ROS production in vitro and in vivo. It will be discussed the target of microRNA and its role in metabolic syndrome.

• International Journal of Oral Biology
• /
• 제40권4호
• /
• pp.197-204
• /
• 2015

MicroRNA (miRNA, miR) is essential in regulating cell differentiation either by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNA in odontoblastic cell differentiation is still unclear. In this study, we examined the molecular mechanism of miR-27-mediated regulation of odontoblast differentiation in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. The results of the present study demonstrated that the miR-27 expression increases significantly during MDPC-23 odontoblastic cell differentiation. Furthermore, miR-27 up-regulation promotes the differentiation of MDPC-23 cells and accelerates mineralization without cell proliferation. The over-expression of miR-27 significantly increased the expression levels of Wnt1 mRNA and protein. In addition, the results of target gene prediction revealed that Wnt1 mRNA has an miR-27 binding site in its 3'UTR, and is increased by miR-27. These results suggested that miR-27 promotes MDPC-23 odontoblastic cell differentiation by targeting Wnt1 signaling. Therefore, miR-27 is a critical odontoblastic differentiation molecular target for the development of miRNA based therapeutic agents in dental medicine.

• Molecules and Cells
• /
• 제45권6호
• /
• pp.365-375
• /
• 2022

Long non-coding RNAs (lncRNAs) may be important regulators in the progression of ankylosing spondylitis (AS). The competing endogenous RNA (ceRNA) activity of lncRNAs plays crucial roles in osteogenesis. We identified the mechanism of the differentially expressed lncRNA MALAT1 in AS using bioinformatic analysis and its ceRNA mechanism. The interaction of MALAT1, microRNA-558, and GSDMD was identified using integrated bioinformatics analysis and validated. Loss- and gain-of-function assays evaluated their effects on the viability, apoptosis, pyroptosis and inflammation of chondrocytes in AS. We found elevated MALAT1 and GSDMD but reduced miR-558 in AS cartilage tissues and chondrocytes. MALAT1 contributed to the suppression of cell viability and facilitated apoptosis and pyroptosis in AS chondrocytes. GSDMD was a potential target gene of miR-558. Depletion of MALAT1 expression elevated miR-558 by inhibiting GSDMD to enhance cell viability and inhibit inflammation, apoptosis and pyroptosis of chondrocytes in AS. In summary, our key findings demonstrated that knockdown of MALAT1 served as a potential suppressor of AS by upregulating miR-558 via the downregulation of GSDMD expression.