• BMB Reports
• /
• v.42 no.11
• /
• 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.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.4
• /
• pp.1575-1579
• /
• 2015

Some microRNAs (miRNAs) have been shown to act as oncogenes or tumor suppressor genes in human melanomas. miR-328 is upregulated in blood cells of melanoma patients compared to in healthy controls. This suggests a role for miR-328 in melanoma that warrants investigation. In this study, we demonstrated miR-328 levels to be dramatically decreased in human melanoma cell lines. Moreover, forced expression of miR-328 inhibited proliferation and induced G1-phase arrest of the SK-MEL-1 melanoma cell line. We identified TGFB2 as a direct target gene for miR-328 using a fluorescent reporter assay and western blotting. Levels of TGFB2 were dramatically increased in human melanoma cell lines and were inversely correlated with the miR-328 expression level. Our findings provide new insights into the mechanisms of human melanoma development, indicating that miR-328 has therapeutic potential for this disease.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.2
• /
• pp.917-923
• /
• 2014

Chondrosarcomas are malignant cartilage-forming tumors of bone which exhibit resistance to both chemotherapy and radiation treatment. miRNAs have been well demonstrated to regulate gene expression and play essential roles in a variety of biological processes, including proliferation, differentiation, migration, cell cycling and apoptosis. In this study, we obtained evidence that miR-100 acts as a tumor suppressor in human chondrosarcomas. Interestingly, cisplatin resistant chondrosarcoma cells exhibit decreased expression of miR-100 compared with parental cells. In addition, we identified mTOR as a direct target of miR-100. Overexpression of miR-100 complementary pairs to the 3' untranslated region (UTR) of mTOR, resulted in sensitization of cisplatin resistant cells to cisplatin. Moreover, recovery of the mTOR pathway by overexpression of S6K desensitized the chondrosarcoma cells to cisplatin, suggesting the miR-100-mediated sensitization to cisplatin dependent on inhibition of mTOR. In summary, the present studies highlight miR-100 as a tumor suppressor in chondrosarcoma contributing to anti-chemoresistance. Overexpression of miR-100 might be exploited as a therapeutic strategy along with cisplatin-based combined chemotherapy for the treatment of clinical chondrosarcoma patients.

• BMB Reports
• /
• v.42 no.8
• /
• pp.493-499
• /
• 2009

MicroRNAs (miRs) are a family of small noncoding RNAs that regulate gene expression by targeting mRNAs in a sequence specific manner, inducing translational repression or mRNA degradation. In this paper we have first analyzed by microarray the miR-profile in erythroid precursor cells from one normal and two thalassemic patients expressing different levels of fetal hemoglobin (one of them displaying HPFH phenotype). The microarray data were confirmed by RT-PCR analysis, and allowed us to identify miR-210 as an highly expressed miR in the erythroid precursor cells from the HPFH patient. When RT-PCR was performed on mithramycin-induced K562 cells and erythroid precursor cells, miR-210 was found to be induced in time-dependent and dose-dependent fashion, together with increased expression of the fetal $\gamma$-globin genes. Altogether, the data suggest that miR-210 might be involved in increased expression of $\gamma$-globin genes in differentiating erythroid cells.

• Journal of Information Technology Applications and Management
• /
• v.30 no.1
• /
• pp.97-114
• /
• 2023

The purpose of this study is to derive practical implications by verifying the influence of MSME owners' leadership type and management performance on knowledge management. In addition, we tried to verify the mediating role of knowledge management between the leadership type and management performance of MSME owners. Leadership types were divided into transformational leadership and transactional leadership. Transformational leadership consisted of charisma and inspirational motivation, while transactional leadership consisted of situational rewards and management by exception. For data collection, we conducted a survey targeting workers in small businesses. After excluding insincere data that were inappropriate for analysis, we used the remaining 243 samples for empirical analysis. To test the hypothesis, we adopted regression analysis and three-step mediated regression analysis as analysis methods. As a result of the empirical analysis, all seven hypotheses derived were supported, and the main results are summarized as follows. First, we found that MSME owners' transformational leadership and transactional leadership had a positive effect on knowledge management and management performance. Second, we found that knowledge management of MSME owners had a positive effect on business performance. Third, both transformational leadership and transactional leadership of MSME owners were found to be partially mediated by knowledge management in relation to management performance. Based on these research results, we derived practical implications for MSME owners.

• Journal of Life Science
• /
• v.24 no.7
• /
• pp.798-803
• /
• 2014

Cathepsin D (CtsD), an aspartyl peptidase, is involved in apoptosis, resulting in the release of cytochrome C from mitochondria in cells. Here, we investigated microRNA regulation of CtsD expression in 3T3-L1 cells First, we observed the expression of CtsD in cells in response to doxorubicin (Dox). As expected, the level of CtsD mRNA was increased in 3T3-L1 cells exposed to Dox in a dose-dependent manner. Cellular viability of ectopically expressed CtsD cells was also decreased. Next, we used the miRanda program to search for particular microRNA targeting CtsD. MiR-145 was selected as a putative controller for CtsD because miR-145 had a high mirSVR score. In a reporter assay, the luciferase activity of cells containing the CtsD 3'-UTR region was decreased in cells transfected with miR-145 mimic compared to that of a control. The level of CtsD expression was down-regulated in preadipocytes ectopically expressing miR-145 and up-regulated by an miR-145 inhibitor. Cells also suppressed miR-145 expression when exposed to Dox. The miR-145 inhibitor reduced the cellular viability of 3T3-L1 cells. Taken together, these data suggest that miR-145 regulates CtsD-mediated cell death in adipocytes. These findings may have valuable implications concerning the molecular mechanism of CtsD-mediated cell death in obesity, suggesting that CtaD could be a useful therapeutic tool for the prevention and treatment of obesity by regulating fat cell numbers.

• IMMUNE NETWORK
• /
• v.11 no.3
• /
• pp.135-154
• /
• 2011

The great discovery of microRNAs (miRNAs) has revolutionized current cell biology and medical science. miRNAs are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region of specific messenger RNAs for degradation or translational repression. New members of the miRNA family are being discovered on a daily basis and emerging evidence has demonstrated that miRNAs play a major role in a wide range of developmental process including cell proliferation, cell cycle, cell differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate, neuronal gene expression, brain morphogenesis, muscle differentiation and stem cell division. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease, and autoimmune disease. Interestingly, in addition, miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from cancer to myocardial infarction. miRNAs can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. As a consequence of extensive participation in normal functions, it is quite logical to ask the question if abnormalities in miRNAs should have importance in human diseases. Great discoveries and rapid progress in the past few years on miRNAs provide the hope that miRNAs will in the near future have a great potential in the diagnosis and treatment of many diseases. Currently, an explosive literature has focussed on the role of miRNA in human cancer and cardiovascular disease. In this review, I briefly summarize the explosive current studies about involvement of miRNA in various human cancers and cardiovascular disease.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2813-2818
• /
• 2012

Background: Considerable evidence suggests that metadherin (MTDH) is a potentially crucial mediator of tumor malignancy and an important therapeutic target for simultaneously enhancing chemotherapy efficacy and reducing metastasis risk. Inhibition of MTDH expression by RNA interference has been shown in several previous research, but silencing MTDH expression by microRNA (miRNA) interference in breast cancer has not been established. In the present study, we investigated the role of MTDH-miRNA in down-regulation of proliferation, motility and migration of breast carcinoma cells. Methods: Expression vectors of recombinant plasmids expressing artificial MTDH miRNA were constructed and transfected to knockdown MTDH expression in MDA-MB-231 breast cancer cells. Expression of MTDH mRNA and protein was detected by RT-PCR and Western blot, respectively. MTT assays were conducted to determine proliferation, and wound healing assays and transwell migration experiments for cell motility and migration. Results: Transfection of recombinant a plasmid of pcDNA-MTDH-miR-4 significantly suppressed the MTDH mRNA and protein levels more than 69% in MDA-MB-231 breast cancer cells. This knockdown significantly inhibited proliferation, motility and migration as compared with controls. Conclusions: MTDH-miRNA may play an important role in down-regulating proliferation, motility and migration in breast cancer cells, and should be considered as a potential small molecule inhibitor therapeutic targeting strategy for the future.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.2
• /
• pp.475-483
• /
• 2015

Genes and microRNAs (miRNAs) have important roles in human oncology. However, most of the biological factors are reported in disperse form which makes it hard to discover the pathology. In this study, genes and miRNAs involved in human endometrial cancer(EC) were collected and formed into regulatory networks following their interactive relations, including miRNAs targeting genes, transcription factors (TFs) regulating miRNAs and miRNAs included in their host genes. Networks are constructed hierarchically at three levels: differentially expressed, related and global. Among the three, the differentially expressed network is the most important and fundamental network that contains the key genes and miRNAs in EC. The target genes, TFs and miRNAs are differentially expressed in EC so that any mutation in them may impact on EC development. Some key pathways in networks were highlighted to analyze how they interactively influence other factors and carcinogenesis. Upstream and downstream pathways of the differentially expressed genes and miRNAs were compared and analyzed. The purpose of this study was to partially reveal the deep regulatory mechanisms in EC using a new method that combines comprehensive genes and miRNAs together with their relationships. It may contribute to cancer prevention and gene therapy of EC.

• Bulletin of the Korean Chemical Society
• /
• v.34 no.3
• /
• pp.735-742
• /
• 2013

Peptide nucleic acids (PNAs) that bind to complementary nucleic acid sequences with extraordinarily high affinity and sequence specificity can be used as antisense oligonucleotides against microRNAs, namely antagomir PNAs. However, methods for efficient cellular delivery must be developed for effective use of PNAs as therapeutic agents. Here, we demonstrate that antagomir PNAs can be delivered to hepatic cells by complementary DNA oligonucleotide and cationic liposomes containing galactosylated ceramide and a novel cationic lipid, DMKE (O,O'-dimyristyl-N-lysyl glutamate), through glycoprotein-mediated endocytosis. An antagomir PNA was designed to target miR-122, which is required for translation of the hepatitis C virus (HCV) genome in hepatocytes, and was hybridized to a DNA oligonucleotide for complexation with cationic liposome. The PNA-DNA hybrid molecules were efficiently internalized into hepatic cells by complexing with the galactosylated cationic liposome in vitro. Galactosylation of liposome significantly enhanced both lipoplex cell binding and PNA delivery to the hepatic cells. After 4-h incubation with galactosylated lipoplexes, PNAs were efficiently delivered into hepatic cells and HCV genome translation was suppressed more than 70% through sequestration of miR-122 in cytoplasm. PNAs were readily released from the PNA-DNA hybrid in the low pH environment of the endosome. The present study indicates that transfection of PNA-DNA hybrid molecules using galactosylated cationic liposomes can be used as an efficient non-viral carrier for antagomir PNAs targeted to hepatocytes.