• Biomedical Science Letters
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• v.29 no.1
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• pp.11-25
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• 2023

In hepatocellular carcinoma (HCC), chromosome 4 open-reading frame 47 (C4orf47) has not been so far investigated for its prognostic value or association with infiltrating immune cells. We performed bioinformatics analysis on HCC data and analyzed the data using online databases such as TIMER, UALCAN, Kaplan-Meier plotter, LinkedOmics, and GEPIA2. We found that C4orf47 expression in HCC was higher compared to normal tissues. High C4orf47 expression was associated with a worse prognosis in HCC. The correlation between C4orf47 and infiltrating immune cells is positively associated with CD4+T cells, B cells, neutrophils, macrophages, and dendritic cells in HCC. Moreover, high C4orf47 expression was correlated with a poor prognosis of infiltrating immune cells. Analysis of C4orf47 gene co-expression networks revealed that 12501 genes were positively correlated with C4orf47, whereas 7200 genes were negatively correlated. The positively related genes of C4orf47 are associated with a high hazard ratio in different types of cancer, including HCC. Regarding the biological functions of C4orf47 gene, it mainly regulates RNA metabolic process, DNA replication, and cell cycle. The C4orf47 gene may play a prognostic role by regulating the global transcriptome process in HCC. Our findings demonstrate that high C4orf47 expression correlates with poor prognosis and tumor-infiltrating immune cells in HCC. We suggest that C4orf47 is a novel prognostic biomarker and potential immune therapeutic target for HCC.

• Animal cells and systems
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• v.3 no.3
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• pp.319-329
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• 1999

Onset of female puberty follows a series of prepubertal cellular and molecular events including changes of synaptic plasticity, synthetic and releasing activity and gene expression. Dramatic increase of gonadal steroid level is one of the most prominent changes before the onset of puberty. Based on the importance of steroid feedback upon the hypothalamus, we adopted an estrogen sterilized rat (ESR) model where 100 ng of 17$\eta$-estradiol were administered into neonatal pubs for 7 days after birth. To identify genes involved in the onset of female puberty, we applied PCR differential display using RNA samples derived from ESR and control rat hypothalami. About 100 out of more than 1000 RNA species examined displayed differential expression patterns between a 60-day old control rat and ESR. Sequence analysis of differentially amplified PCR products showed homology with genes such as mouse kinesin superfamily-associated protein 3 (KAP3) and several cDNAs previously described by others in mouse and human tissues. Several gene products such as 2-1 and 8-1 corresponded to novel DNA sequences. We analyzed mRNA levels of KAP3, 2-1 and 8-1 genes in the hypothalami derived from neonatal, 6-, 28-, 31-, and 40-day old rats. Northern blot analysis showed that mRNAs of KAP3, 2-1 and 8-1 genes were markedly increased before the initiation of puberty. Neonatal treatment of estrogen clearly inhibited prepubertal increases in KAP3, 2-1 and 8-1 mRNA levels. Therefore, these genes may play important roles in the initiation of hypothalamic puberty. In addition, intracerebroventricular (icv) injection of antisense KAP3 oligodeoxynucleotide (ODN) clearly delayed puberty initiation determined by vaginal opening, which further confirmed that KAP3 plays an important role in the regulation of puberty initiation.

• Molecules and Cells
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• v.24 no.3
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• pp.394-408
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• 2007

Several genes/QTLs governing resistance/tolerance to abiotic and biotic stresses have been reported and mapped in rice. A QTL for submergence tolerance was found to be co-located with a major QTL for broad-spectrum bacterial leaf blight (bs-blb) resistance on the long arm of chromosome 5 in indica cultivars FR13A and IET8585. Using the Nipponbare (japonica) and 93-11 (indica) genome sequences, we identified, in silico, candidate genes in the chromosomal region [Kottapalli et al. (2006)]. Transcriptional profiling of FR13A and IET8585 using a rice 22K oligo array validated the above findings. Based on in silico analysis and arraying we observed that both cultivars respond to the above stresses through a common signaling system involving protein kinases, adenosine mono phosphate kinase, leucine rich repeat, PDZ/DHR/GLGF, and response regulator receiver protein. The combined approaches suggest that transcription factor EREBP on long arm of chromosome 5 regulates both submergence tolerance and blb resistance. Pyruvate decarboxylase and alcohol dehydrogenase, co-located in the same region, are candidate downstream genes for submergence tolerance at the seedling stage, and t-snare for bs-blb resistance. We also detected up-regulation of novel defense/stress-related genes including those encoding fumaryl aceto acetate (FAA) hydrolase, scramblase, and galactose oxidase, in response to the imposed stresses.

• Tuberculosis and Respiratory Diseases
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• v.79 no.2
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• pp.85-90
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• 2016

Background: Lung cancer is the most common cause of cancer related death. Alterations in gene sequence, structure, and expression have an important role in the pathogenesis of lung cancer. Fusion genes and alternative splicing of cancer-related genes have the potential to be oncogenic. In the current study, we performed RNA-sequencing (RNA-seq) to investigate potential fusion genes and alternative splicing in non-small cell lung cancer. Methods: RNA was isolated from lung tissues obtained from 86 subjects with lung cancer. The RNA samples from lung cancer and normal tissues were processed with RNA-seq using the HiSeq 2000 system. Fusion genes were evaluated using Defuse and ChimeraScan. Candidate fusion transcripts were validated by Sanger sequencing. Alternative splicing was analyzed using multivariate analysis of transcript sequencing and validated using quantitative real time polymerase chain reaction. Results: RNA-seq data identified oncogenic fusion genes EML4-ALK and SLC34A2-ROS1 in three of 86 normal-cancer paired samples. Nine distinct fusion transcripts were selected using DeFuse and ChimeraScan; of which, four fusion transcripts were validated by Sanger sequencing. In 33 squamous cell carcinoma, 29 tumor specific skipped exon events and six mutually exclusive exon events were identified. ITGB4 and PYCR1 were top genes that showed significant tumor specific splice variants. Conclusion: In conclusion, RNA-seq data identified novel potential fusion transcripts and splice variants. Further evaluation of their functional significance in the pathogenesis of lung cancer is required.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.75-75
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• 2003

Transition of the resting primordial follicle to the growing primary follicle is a critical process for female reproduction, but its mechanism is poorly understood. The present study was conducted to investigate gene expression profile at the primordial-primary follicle transition process. We isolated total RNA of female mouse ovary at day1 (contains only primordial follicles) and day5 (contains primordial and primary follicles) and synthesized cDNA using annealing control primers (ACP; Seegene, Inc., Seoul, Korea). ACP provides annealing specificity and sensitivity to the template and allows to identify only authentic differentially expressed genes (DEGs). We used total 80 ACPs for PCR, observed PCR products on 2% agarose gel, cloned 42 DEGs using TOPO TA cloning vector, sequenced, and analyzed by BLAST search. Sequences of 34 clones significantly matched database entries while 4 clones were novel and 4 clones were EST. Two of 34 genes were specifically expressed only in day 5 ovaries (Sui1-rs1, Apg3p/Aut1p-like), and rest of 32 genes were expressed in both stages but were differential in amount. Differential expression was confirmed using semiquantitative RT-PCR, and there was no false positive. Anx11 and Pepp2-pending were highly expressed genes in day1-, while BPOZ, Ches1, Kcmf1, NHE3, Nid2, Ninj1, SENP3 and Survivin were highly expressed genes in day5-ovary. List of genes would provide insight for further study of mechanism regulating primordial-primary follicle transition.

• BMB Reports
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• v.33 no.5
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• pp.396-401
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• 2000

A differential display method is used to identify novel genes whose expression is affected by treatment with ferric ammonium citrate (FAC) or desferrioxamine (DFO), an iron chelating agent in the human hepatoblastoma cell line (HepG2). These chemicals are known to deplete or increase the intracellular concentration of iron, respectively. Initially, we isolated seventeen genes whose expressions are down- or up regulated by the treatment of the chemicals, as well as their four differentially expressed genes that are designated as clone-1, -2, -3, and -4. These are further characterized by cDNA sequencing and Northern blot analysis. Through the cDNA sequencing, as well as comparing them to genes published using the NCBI BLAST program, we identified the sequence of the clone-1 that is up-regulated by the treatment of DFO. It is identical to the human insulin-like growth factor binding protein-1 (IGFBP-1). This suggests that the IGFBP-1 gene in the HepG2 cell is up-regulated by an iron depletion condition. Also, the expression of the clone-3 and -4 is up-regulated by FAC treatment and their eDNA sequences are identical to the human ferritin-fight chain and human NADH-dehydrogenase, respectively. However, the sequence of the clone-2 has no significant homology to any other known gene. Therefore, we suggest that changes of the cellular iron level in the HepG2 cell affects the transcription of cellular genes. This includes human IGFBP-1, ferritin-fight chain, and NADH-dehydrogenase. Regulation of these gene expressions may have an important role in cellular functions that are related to cellular iron metabolism.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.10a
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• pp.114-114
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• 2018

Among the various volatile organic compounds (VOCs) emitted by the plant, floral scent plays a key role in attracting pollinators for reproduction and mediates ecological interactions. Floral scent is an important trait and industry drives the competition for flowers with novel scents. Chrysanthemum is one of the well-known ornamental plants and is a popular cut flower across the world. Floral scent and the genes responsible for the floral scent emission are poorly studied in chrysanthemum. In the present study, floral scent and the expression pattern of floral scent genes were analyzed in two chrysanthemum cultivars 'Golden Egg' and 'Gaya Glory'. Initially, intensity of the floral scent in five developing stages of flower including 'budding (B), bud developing (BD), initial blooming (IB), almost open (AO) and open flower (OF)' was analyzed using electronic nose (E-nose) with six metal oxide sensors. Based on the distance analysis, different stages of flower showed different relative intensity of scent according to the sensory evaluation. Although the scent pattern differed by stage, scent intensity was strongest in the OF stage in the completely opened flower in both the cultivars. Further, expression pattern of six genes in the floral scent pathway including FDS, IDI, ISPH, TPS2, TPS5 and TPS6 was observed in all the five stages of the flower in both the cultivars. The expression pattern of all the six genes differed by stage and the terpene synthase genes TPS2, TPS5 and TPS6 showed good expression levels in the $5^{th}$ flower stage compared to other stages. This study provides a preliminary data for understanding the regulation of floral scent in chrysanthemum.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.457-463
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• 2015

The pathogenesis of mantle cell lymphoma, a special subtype of lymphoma that is invasive and indolent and has a median survival of 3 to 4 years, is still partially unexplained. Much research about genes and miRNAs has been conducted in recent years, but interactions and regulatory relations of genetic elements which may play a vital role in genesis of MCL have attracted only limited attention. The present study concentrated on regulatory relations about genes and miRNAs contributing to MCL pathogenesis. Numerous experimentally validated raw data were organized into three topology networks, comprising differentially expressed, associated and global examples. Comparison of similarities and dissimilarities of the three regulating networks, paired with the analysis of the interactions between pairs of elements in every network, revealed that the differentially expressed network illuminated the carcinogenicity mechanism of MCL and the related network further described the regulatory relations involved, including prevention, diagnosis, development and therapy. Three kinds of regulatory relations for host genes including miRNAs, miRNAs targeting genes and genes regulating miRNAs were concluded macroscopically. Regulation of the differentially expressed miRNAs was also analyzed, in terms of abnormal gene expression affecting the MCL pathogenesis. Special regulatory relations were uncovered. For example, auto-regulatory loops were found in the three topology networks, key pathways of the nodes being highlighted. The present study focused on a novel point of view revealing important influencing factors for MCL pathogenesis.

• Biomedical Science Letters
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• v.21 no.4
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• pp.181-187
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• 2015

Osteoporosis is one of the diseases caused by accumulation of effects from complex interactions between genetic and environmental factors. Aging is the major cause for osteoporosis, which normally increases skeletal fragility and bone fracture especially among the elder. "Omics" refers to a specialized research field dealing with high-throughput biological data, such as genomics, transcriptomics, proteomics or metabolomics. Integration of data from multi-omics has been approved to be a powerful strategy to colligate biological phenomenon with multiple aspects. Actually, integrative analyses of "omics" datasets were used to present pathogenesis of specific diseases or casual biomarkers including susceptible genes. In this study, we evaluated the proposed relationship of novel susceptible genes (TREML2, HTR1E, and GLO1) with osteoporosis, which genes were obtained using multi-omics integration analyses. To this end, SNPs of the susceptible genes in the Korean female cohort were analyzed. As a result, one SNP of HTR1E and five SNPs of TREML2 were identified to associate with osteoporosis. The highest significant SNP was $rs6938076^*$ of TREML2 (OR=0.63, CI: 0.45~0.89, recessive P=0.009). Consequently, the susceptible genes identified through the multi-omics analyses were confirmed to have association with osteoporosis. Therefore, multi-omics analysis might be a powerful tool to find new genes associated with a disease. We further identified that TREML2 has more associated with osteoporosis in females than did HTR1E.

• Molecules and Cells
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• v.24 no.1
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• pp.45-59
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• 2007

We describe the gene expression profile of third leaves of rice (cv. Nipponbare) seedlings subjected to salt stress (130 mM NaCl). Transcripts of Mn-SOD, Cu/Zn-SOD, cytosolic and stromal APX, GR and CatB were up-regulated, whereas expression of thylakoid-bound APX and CatA were down-regulated. The levels of the compatible solute proline and of transcripts of its biosynthetic gene, ${\Delta}^1$-pyrroline-5-carboxylate synthetase (P5CS), were strongly increased by salt stress. Interestingly, a potential compatible solute, ${\gamma}$-aminobutyric acid (GABA), was also found to be strongly induced by salt stress along with marked up-regulation of transcripts of GABA-transaminase. A dye-swap rice DNA microarray analysis identified a large number of genes whose expression in third leaves was altered by salt stress. Among 149 genes whose expression was altered at all the times assayed (3, 4 and 6 days) during salt stress, there were 47 annotated novel genes and 76 unknown genes. These results provide new insight into the effect of salt stress on the expression of genes related to antioxidant enzymes, proline and GABA as well as of genes in several functional categories.