• Asian Pacific Journal of Cancer Prevention
• /
• 제16권4호
• /
• 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.

• Clinical and Experimental Reproductive Medicine
• /
• 제48권3호
• /
• pp.245-254
• /
• 2021

Objective: In humans, polycystic ovary syndrome (PCOS) is an androgen-dependent ovarian disorder. Aberrant gene expression in folliculogenesis can arrest the transition of preantral to antral follicles, leading to PCOS. We explored the possible role of altered gene expression in preantral follicles of estradiol valerate (EV) induced polycystic ovaries (PCO) in a mouse model. Methods: Twenty female balb/c mice (8 weeks, 20.0±1.5 g) were grouped into control and PCO groups. PCO was induced by intramuscular EV injection. After 8 weeks, the animals were killed by cervical dislocation. Blood serum (for hormonal assessments using the enzyme-linked immunosorbent assay technique) was aspirated, and ovaries (the right ovary for histological examinations and the left for quantitative real-time polymerase) were dissected. Results: Compared to the control group, the PCO group showed significantly lower values for the mean body weight, number of preantral and antral follicles, serum levels of estradiol, luteinizing hormone, testosterone, and follicle-stimulating hormone, and gene expression of TGFB1, GDF9 and BMPR2 (p<0.05). Serum progesterone levels were significantly higher in the PCO animals than in the control group (p<0.05). No significant between-group differences (p>0.05) were found in BMP6 or BMP15 expression. Conclusion: In animals with EV-induced PCO, the preantral follicles did not develop into antral follicles. In this mouse model, the gene expression of TGFB1, GDF9, and BMPR2 was lower in preantral follicles, which is probably related to the pathologic conditions of PCO. Hypoandrogenism was also detected in this EV-induced murine PCO model.

• Asian-Australasian Journal of Animal Sciences
• /
• 제30권11호
• /
• pp.1529-1539
• /
• 2017

Objective: The objective of this study was to compare the DNA methylation profile in the longissimus dorsi muscle between Small Tailed Han and Dorper${\times}$Small Tailed Han crossbred sheep which were known to exhibit significant difference in meat-production. Methods: Six samples (three in each group) were subjected to the methylated DNA immunoprecipitation sequencing (MeDIP-seq) and subsequent bioinformatics analyses to detect differentially methylated regions (DMRs) between the two groups. Results: 23.08 Gb clean data from six samples were generated and 808 DMRs were identified in gene body or their neighboring up/downstream regions. Compared with Small Tailed Han sheep, we observed a tendency toward a global loss of DNA methylation in these DMRs in the crossbred group. Gene ontology enrichment analysis found several gene sets which were hypomethylated in gene-body region, including nucleoside binding, motor activity, phospholipid binding and cell junction. Numerous genes were found to be differentially methylated between the two groups with several genes significantly differentially methylated, including transforming growth factor beta 3 (TGFB3), acyl-CoA synthetase long chain family member 1 (ACSL1), ryanodine receptor 1 (RYR1), acyl-CoA oxidase 2 (ACOX2), peroxisome proliferator activated receptor-gamma2 (PPARG2), netrin 1 (NTN1), ras and rab interactor 2 (RIN2), microtubule associated protein RP/EB family member 1 (MAPRE1), ADAM metallopeptidase with thrombospondin type 1 motif 2 (ADAMTS2), myomesin 1 (MYOM1), zinc finger, DHHC type containing 13 (ZDHHC13), and SH3 and PX domains 2B (SH3PXD2B). The real-time quantitative polymerase chain reaction validation showed that the 12 genes are differentially expressed between the two groups. Conclusion: In the current study, a tendency to a global loss of DNA methylation in these DMRs in the crossbred group was found. Twelve genes, TGFB3, ACSL1, RYR1, ACOX2, PPARG2, NTN1, RIN2, MAPRE1, ADAMTS2, MYOM1, ZDHHC13, and SH3PXD2B, were found to be differentially methylated between the two groups by gene ontology enrichment analysis. There are differences in the expression of 12 genes, of which ACSL1, RIN2, and ADAMTS2 have a negative correlation with methylation levels and the data suggest that DNA methylation levels in DMRs of the 3 genes may have an influence on the expression. These results will serve as a valuable resource for DNA methylation investigations on screening candidate genes which might be related to meat production in sheep.

• Asian Pacific Journal of Cancer Prevention
• /
• 제13권8호
• /
• pp.3681-3685
• /
• 2012

Background: In breast cancer, estrogen receptors have been demonstrated to interact with transcription factors to regulate target gene expression. However, high-throughput identification of the transcription regulation relationship between transcription factors and their target genes in response to estradiol is still in its infancy. Purpose: Thus, the objective of our study was to interpret the transcription regulation network of MCF7 breast cancer cells exposed to estradiol. Methods: In this work, GSE11352 microarray data were used to identify differentially expressed genes (DEGs). Results: Our results showed that the MYB (v-myb myeloblastosis viral oncogene homolog [avian]), PGR (progesterone receptor), and MYC (v-myc myelocytomatosis viral oncogene homolog [avian]) were hub nodes in our transcriptome network, which may interact with ER and, in turn, regulate target gene expression. MYB can up-regulate MCM3 (minichromosome maintenance 3) and MCM7 expression; PGR can suppress BCL2 (B-cell lymphoma 2) expression; MYC can inhibit TGFB2 (transforming growth factor, beta 2) expression. These genes are associated with breast cancer progression via cell cycling and the $TGF{\beta}$ signaling pathway. Conclusion: Analysis of transcriptional regulation may provide a better understanding of molecular mechanisms and clues to potential therapeutic targets in the treatment of breast cancer.

• Genomics & Informatics
• /
• 제7권2호
• /
• pp.85-96
• /
• 2009

The differentiation of neural precursor cells (NPCs) into neurons and astrocytes is a process that is tightly controlled by complicated and ill-defined gene networks. To extend our knowledge to gene networks, we performed a temporal analysis of gene expression during the differentiation (2, 4, and 8 days) of spinal cord-derived NPCs using oligonucleotide microarray technology. Out of 32,996 genes analyzed, 1878 exhibited significant changes in expression level (fold change>2, p<0.05) at least once throughout the differentiation process. These 1878 genes were classified into 12 groups by k-means clustering, based on their expression patterns. K-means clustering analysis revealed that the genes involved in astrogenesis were categorized into the clusters containing constantly upregulated genes, whereas the genes involved in neurogenesis were grouped to the cluster showing a sudden decrease in gene expression on Day 8. Functional analysis of the differentially expressed genes indicated the enrichment of genes for Pax6- NeuroD signaling.TGFb-SMAD and BMP-SMAD.which suggest the implication of these genes in the differentiation of NPCs and, in particular, key roles for Nova1 and TGFBR1 in the neurogenesis/astrogenesis of mouse spinal cord.

• Genomics & Informatics
• /
• 제8권1호
• /
• pp.34-40
• /
• 2010

Radiofrequency (RF) radiation might induce the transcription of a certain set of genes as other physical stresses like ionizing radiation and UV. To observe transcriptional changes upon RF radiation, we exposed WI-38, human lung fibroblast cell to 1763 MHz of mobile phone RF radiation at 60 W/kg of specific absorption rate (SAR) for 24h with or without heat control. There were no significant changes in cell numbers and morphology after exposure to RF radiation. Using quantitative RT-PCR, we checked the expression of three heat shock protein (HSP) (HSPA1A, HSPA6 and HSP105) and seven stress-related genes (TNFRSF11B, FGF2, TGFB2, ITGA2, BRIP1, EXO1, and MCM10) in RF only and RF/HS groups of RF-exposed cells. The expressions of three heat shock proteins and seven stress-related genes were selectively changed only in RF/HS groups. Based on the expression of ten genes, we could classify thermal and non-thermal effect of RF-exposure, which genes can be used as biomarkers for RF radiation exposure.

• 대한의생명과학회지
• /
• 제15권3호
• /
• pp.261-263
• /
• 2009

Methylprednisolone is a synthetic glucocorticoid which is usually taken intravenously for many neurosurgical diseases which cause edema including brain tumor, and trauma including spinal cord injury. Methylprednisolone reduces swelling and decreases the body's immune response. It is also used to treat many immune and allergic disorders, such as arthritis, lupus, psoriasis, asthma, ulcerative colitis, and Crohn's disease. To identify genes expressed during methylprednisolone treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up- or down-regulated genes) which are methylprednisolone differentially expressed in neurons. Lipocalin 3 is the gene most significantly increased among 772 up-regulated genes (more than 2 fold over-expression) and Aristaless 3 is the gene most dramatically decreased among 959 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Fgb, Thbd, Cfi, F3, Kngl, Serpinel, C3, Tnfrsf4 and Il8rb are involved stress-response gene, and Nfkbia, Casp7, Pik3rl, I11b, Unc5a, Tgfb2, Kitl and Fgf15 are strongly associated with development. Cell cycle associated genes (Mcm6, Ccnb2, Plk1, Ccnd1, E2f1, Cdc2a, Tgfa, Dusp6, Id3) and cell proliferation associated genes (Ccl2, Tnfsf13, Csf2, Kit, Pim1, Nr3c1, Chrm4, Fosl1, Spp1) are down-regulated more than 2 times by methylprednisolone treatment. Among the genes described above, 4 up-regulated genes are confirmed those expression by RT-PCR. We found that methylprednisolone is related to expression of many genes associated with stress response, development, cell cycle, and cell proliferation by DNA microarray analysis. However, We think further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by methylprednisolone. The resulting data will give the one of the good clues for understanding of methylprednisolone under molecular level in the neurons.

• 대한의생명과학회지
• /
• 제15권1호
• /
• pp.97-99
• /
• 2009

Geldanamycin is a benzoquinone ansamycin antibiotic that binds to cytosol HSP90 (Heat Shock Protein 90) and changes its biological function. HSP90 is involved in the intracellular important roles for the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis. To identify genes expressed during geldanamycin treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up-or down-regulated genes) which are geldanamycin differentially expressed in neurons. Granzyme B is the gene most significantly increased among 204 up-regulated genes (more than 2 fold over-expression) and Chemokine (C-C motif) ligand 20 is the gene most dramatically decreased among 491 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Cxc110, Cyp11a1, Gadd45a, Gja1, Gpx2, Ifua4, Inpp5e, Sox4, and Stip1 are involved stress-response gene, and Cryab, Dnaja1, Hspa1a, Hspa8, Hspca, Hspcb, Hspd1, Hspd1, and Hsph1 are strongly associated with protein folding. Cell cycle associated genes (Bc13, Brca2, Ccnf, Cdk2, Ddit3, Dusp6, E2f1, Illa, and Junb) and inflammatory response associated genes (Cc12, Cc120, Cxc12, Il23a, Nos2, Nppb, Tgfb1, Tlr2, and Tnt) are down-regulated more than 2 times by geldanamycin treatment. We found that geldanamycin is related to expression of many genes associated with stress response, protein folding, cell cycle, and inflammation by DNA microarray analysis. Further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by geldanamycin. The resulting data will give the one of the good clues for understanding of geldanamycin under molecular level in the neurons.

• Toxicological Research
• /
• 제34권3호
• /
• pp.241-247
• /
• 2018

Lactobacillus (LAB) have been reported to exert both harmful and beneficial effects on human and animal health. Recently, it has been reported that dysbiosis and bacterial translocation contribute to liver fibrosis. However, the role of Gram-positive LAB in the situation of chronic liver diseases has not been yet elucidated. Liver injury was induced by bile duct ligation (BDL) in LAB or control-administered mice. Liver fibrosis was enhanced in LAB-administered mice compared with control-treated mice as demonstrated by quantification of Sirius-red positive area, hydroxyproline contents and fibrosis-related genes ($Col1{\alpha}1$, Acta2, Timp1, Tgfb1). Moreover, LAB-administered mice were more susceptible to BDL-induced liver injury as shown by increased ALT and AST level of LAB group compared with control group at 5 days post BDL. Consistent with serum level, inflammatory cytokines ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) were also significantly increased in LAB-treated mice. Of note, LAB-treated liver showed increased lipoteichoic acid (LTA) expression compared with control-treated liver, indicating that LAB-derived LTA may translocate from intestine to liver via portal vein. Indeed, responsible receptor or inflammatory factor (PAFR and iNOS) for LTA were upregulated in LAB-administered group. The present findings demonstrate that administration of LAB increases LTA translocation to liver and induces profibrogenic inflammatory milieu, leading to aggravation of liver fibrosis. The current study provides new cautious information of LAB for liver fibrosis patients to prevent the detrimental effect of LAB supplements.

• Journal of the Korean Data and Information Science Society
• /
• 제25권5호
• /
• pp.1095-1106
• /
• 2014

본 연구에서는 악성간암환자의 생존기간에 영향을 주는 인자를 찾기 위하여 반응변수를 악성간암 환자의 생존을 임상변수의 정보와 SNP유전인자를 통합한 자료를 대상으로 이해하기 쉬운 나무구조 생존모형과 심볼릭자료분석을 실시하여 영향을 주는 유의한 인자 뿐 아니라 그 임계치를 구하여 임상적으로 유용한 결과를 찾아 임상에 적용하는 것이 목적이다. 악성간암환자의 임상자료를 계량화하여 통계적 예후진단 모형을 구함으로써 임상변수 간 숨겨진 변수간의 관계를 규명하고 생존기간 군에 따른 예측 분류모형을 구하여 현시적으로 진단후 예후에 영향을 주는 중요 임상변수와 유전체변수 그 임계치를 구하여 임상에서의 치료계획에 중요한 근거를 제시했다. 심볼릭데이터 분석 결과 정상, 만성 간염, 간염, 악성간염 등의 4개 군으로 구성된 1840명의 대상자를 분석 5 유전체의 20개 SNP가 밝혀진 바 있다. 즉 IL10-ht2가 악성간암의 발병에 매위 강한 관련이 있고 TGFB L10P-Prosms가 만성 간염 환자 중 악성간암 발생 위험을 줄여주는 유전체로 밝혀졌다. SNP변수와 질병군의 컴셉트 변수에 따라 상관정도를 원의 반지름 길이로 상대적으로 나타내 줌으로써 가장 판별력 있는 심볼릭변수를 상대적으로 비교할 수 있었다. 임상자료와 유전체자료를 통합하여 심볼릭 나무구조 생존모형을 구하여 생존기간을 군으로 한 나무구조모형을 유의한 변수와 기준치와 함께 구할 수 있었다.