• Biomolecules & Therapeutics
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• 제27권6호
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• pp.591-602
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• 2019

Human breast cancer cell line, MDA-MB-231, is highly invasive and aggressive, compared to less invasive cell line, MCF-7. To explore the genes that might influence the malignancy of MDA-MB-231, DNA microarray analysis was performed. The results showed that G0/G1 switch 2 (G0S2) was one of the most highly expressed genes among the genes upregulated in MDA-MB-231. Although G0S2 acts as a direct inhibitor of adipose triglyceride lipase, action of G0S2 in cancer progression is not yet understood. To investigate whether G0S2 affects invasiveness of MDA-MB-231 cells, G0S2 expression was inhibited using siRNA, which led to decreased cell proliferation, migration, and invasion of MDA-MB-231 cells. Consequently, G0S2 inhibition inactivated integrin-regulated FAK-Src signaling, which promoted Hippo signaling and inactivated ERK1/2 signaling. In addition, G0S2 downregulation decreased ${\beta}$-catenin expression, while E-cadherin expression was increased. It was demonstrated for the first time that G0S2 mediates the Hippo pathway and induces epithelial to mesenchymal transition (EMT). Taken together, our results suggest that G0S2 is a major factor contributing to cell survival and metastasis of MDA-MB-231 cells.

• Clinical and Experimental Reproductive Medicine
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• 제48권4호
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• pp.337-346
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• 2021

Objective: Red ginseng (RG) exerts anti-inflammatory, anti-proliferative, and immunomodulatory effects on endometriosis through the regulation of microRNA (miRNA) expression. It may also ameliorate endometriosis by affecting the expression of multiple miRNAs simultaneously, rather than acting on a single miRNA at a given time. Since studies on the overall effects of RG on endometriosis via the regulation of miRNA expression are lacking, the current study aimed to explore the global effect of RG on miRNA expression in a mouse model of endometriosis. Methods: To establish the mouse model, the uterine horn of donor mice was implanted into the lateral side of the recipients' peritoneum, followed by vehicle or RG treatment for 8 weeks. Results: To confirm the effects of RG on the established mouse model, the size of the implanted uterus was measured; it was found to be lower in mice from the RG group than in mice from the control group. miRNA expression profiles in the implanted uterus of the mouse model of endometriosis after vehicle or RG administration were analyzed using microarray technology. Thereafter, seven candidate miRNAs and 125 candidate genes (miRNA targets) were identified through a bioinformatics analysis. Conclusion: The present findings suggest that RG regulates the expression of multiple miRNAs and mRNAs, thereby alleviating endometriosis in a mouse model of the disease.

• Genes and Genomics
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• 제40권11호
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• pp.1199-1211
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• 2018

Soil acidification is one of major problems limiting crop growth and especially becoming increasingly serious in China owing to excessive use of nitrogen fertilizer. Only the STOP1 of Arabidopsis was identified clearly sensitive to proton rhizotoxicity and the molecular mechanism for proton toxicity tolerance of plants is still poorly understood. The main objective of this study was to investigate the transcriptomic change in plants under the low pH stress. The low pH as a single factor was employed to induce the response of the wheat seedling roots. Wheat cDNA microarray was used to identify differentially expressed genes (DEGs). A total of 1057 DEGs were identified, of which 761 genes were up-regulated and 296 were down-regulated. The greater percentage of up-regulated genes involved in developmental processes, immune system processes, multi-organism processes, positive regulation of biological processes and metabolic processes of the biological processes. The more proportion of down-regulation genes belong to the molecular function category including transporter activity, antioxidant activity and molecular transducer activity and to the extracellular region of the cellular components category. Moreover, most genes among 41 genes involved in ion binding, 17 WAKY transcription factor genes and 17 genes related to transport activity were up-regulated. KEGG analysis showed that the jasmonate signal transduction and flavonoid biosynthesis might play important roles in response to the low pH stress in wheat seedling roots. Based on the data, it is can be deduced that WRKY transcription factors might play a critical role in the transcriptional regulation, and the alkalifying of the rhizosphere might be the earliest response process to low pH stress in wheat seedling roots. These results provide a basis to reveal the molecular mechanism of proton toxicity tolerance in plants.

• 한국육종학회지
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• 제43권1호
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• pp.1-13
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• 2011

Low temperature stress is one of the major negative factors affecting vegetative and reproductive growth of rice. To better understand responses of rice plants to low temperature we analyzed transcriptome expression patterns in glumous flower of cold-tolerant japonica rice variety, Stejaree45, and cold-susceptible variety, HR19621-AC6 at booting stage under cold water irrigation. A total of 2,411 probes were differentially expressed by low temperature in glumous flowers of the two varieties. Some important genes involved in hormone biosynthesis showed variety-specific regulation. Expression of GA20ox3 and GA2ox, among the genes involved in GA biosynthesis, was regulated differentially in the two varieties. Among the genes involved in IAA biosynthesis, YUCCA1 and TAA1:1 showed variety-specific regulation. Among the genes involved in cytokinin biosynthsis and signaling, expression of LOG, HK1 and HK3 was significantly down-regulated only in the cold-susceptible variety. Among the genes involved in ABA biosynthesis, NSY and AAO3 were down-regulated only in the cold-tolerant variety. In general, genes involved in GA, IAA and cytokinin biosynthesis responded to cold temperature in such a way that capacity of those bioactive hormones is maintained at relatively higher levels under cold temperature in the cold-tolerant variety, which can help minimize cold stress imposed to developing reproductive organs in the cold-tolerant variety.

• Molecules and Cells
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• 제42권2호
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• pp.183-188
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• 2019

Osteoarthritis (OA) is a naturally occurring, irreversible disorder and a major health burden. The disease is multifactorial, involving both physiological and mechanical processes, but calcium crystals have been associated intimately with its pathogenesis. This study tested the hypothesis that these crystals have a detrimental effect on the differentiation of osteoclasts and bone homeostasis. This study employed an osteoblastosteoclast coculture system that resembles in vivo osteoblastdependent osteoclast differentiation along with $Ca^{2+}$-phosphate-coated culture dishes. The calcium-containing crystals upregulated the expression of RANKL and increased the differentiation of osteoclasts significantly as a result. On the other hand, osteoblast differentiation was unaffected. MicroRNA profiling showed that dual-specificity phosphatases 1 (DUSP1) was associated with the increased RANKL expression. DUSP1 belongs to a family of MAPK phosphatases and is known to inactivate all three groups of MAPKs, p38, JNK, and ERK. Furthermore, knockdown of DUSP1 gene expression suggested that RANKL expression increases significantly in the absence of DUSP1 regulation. Microarray analysis of the DUSP1 mRNA levels in patients with pathological bone diseases also showed that the downregulated DUSP1 expression leads to increased expression of RANKL and consequently to the destruction of the bone observed in these patients. These findings suggest that calcium-containing crystals may play a crucial role in promoting RANKL-induced osteoclastogenesis via DUSP1.

• Biomolecules & Therapeutics
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• 제27권1호
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• pp.107-116
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• 2019

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin's but not resveratrol's anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.

• Molecules and Cells
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• 제42권4호
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• pp.321-332
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• 2019

The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-${\beta}$ (TGF-${\beta}$)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.

• Yonsei Medical Journal
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• 제59권9호
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• pp.1041-1048
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• 2018

Purpose: Heat shock factor 1 (HSF1) is a key regulator of the heat shock response and plays an important role in various cancers. However, the role of HSF1 in gastric cancer is still unknown. The present study evaluated the function of HSF1 and related mechanisms in gastric cancer. Materials and Methods: The expression levels of HSF1 in normal and gastric cancer tissues were compared using cDNA microarray data from the NCBI Gene Expression Omnibus (GEO) dataset. The proliferation of gastric cancer cells was analyzed using the WST assay. Transwell migration and invasion assays were used to evaluate the migration and invasion abilities of gastric cancer cells. Protein levels of HSF1 were analyzed using immunohistochemical staining of tissue microarrays from patients with gastric cancer. Results: HSF1 expression was significantly higher in gastric cancer tissue than in normal tissue. Knockdown of HSF1 reduced the proliferation, migration, and invasion of gastric cancer cells, while HSF1 overexpression promoted proliferation, migration, and invasion of gastric cancer cells. Furthermore, HSF1 promoted the proliferation of gastric cancer cells in vivo. In Kaplan-Meier analysis, high levels of HSF1 were associated with poor prognosis for patients with gastric cancer (p=0.028). Conclusion: HSF1 may be closely associated with the proliferation and motility of gastric cancer cells and poor prognosis of patients with gastric cancer. Accordingly, HSF1 could serve as a prognostic marker for gastric cancer.

• BMB Reports
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• 제54권10호
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• pp.497-504
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• 2021

EGR1 (early growth response 1) is dysregulated in many cancers and exhibits both tumor suppressor and promoter activities, making it an appealing target for cancer therapy. Here, we used a systematic multi-omics analysis to review the expression of EGR1 and its role in regulating clinical outcomes in breast cancer (BC). EGR1 expression, its promoter methylation, and protein expression pattern were assessed using various publicly available tools. COSMIC-based somatic mutations and cBioPortal-based copy number alterations were analyzed, and the prognostic roles of EGR1 in BC were determined using Prognoscan and Kaplan-Meier Plotter. We also used bc-GenEx-Miner to investigate the EGR1 co-expression profile. EGR1 was more often downregulated in BC tissues than in normal breast tissue, and its knockdown was positively correlated with poor survival. Low EGR1 expression levels were also associated with increased risk of ER+, PR+, and HER2- BCs. High positive correlations were observed among EGR1, DUSP1, FOS, FOSB, CYR61, and JUN mRNA expression in BC tissue. This systematic review suggested that EGR1 expression may serve as a prognostic marker for BC patients and that clinicopathological parameters influence its prognostic utility. In addition to EGR1, DUSP1, FOS, FOSB, CYR61, and JUN can jointly be considered prognostic indicators for BC.

• Journal of Genetic Medicine
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• 제18권2호
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• pp.110-116
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• 2021

Microdeletions of chromosome 22q11.2 are one of the most common microdeletions occurring in humans, and is known to be associated with a wide range of highly variable features. These deletions occur within a cluster of low copy repeats (LCRs) in 22q11.2, referred to as LCR22 A-H. DiGeorge (DGS)/velocardiofacial syndrome is the most prevalent form of a 22q11.2 deletions, caused by mainly proximal deletions between LCR22 A and D. As deletions of distal portion to the DGS deleted regions has been extensively studied, the recurrent distal 22q11.2 microdeletions distinct from DGS has been suggested as several clinical entities according to the various in size and position of the deletions on LCRs. We report a case of long-term follow-up of a female diagnosed with a 22q11.2 distal deletion syndrome, identified a deletion of 1.9 Mb at 22q11.21q11.23 (chr22: 21,798,906-23,653,963) using single nucleotide polymorphism array. This region was categorized as distal deletion type of 22q11.2, involving LCR22 D-F. She was born as a preterm, low birth weight to healthy non-consanguineous Korean parents. She showed developmental delay, growth retardation, dysmorphic facial features, and mild skeletal deformities. The patient underwent a growth hormone administration due to growth impairment without catch-up growth. While a height gain was noted, she had become overweight and was subsequently diagnosed with pre-diabetes. Our case could help broaden the genetic and clinical spectrum of 22q11.2 distal deletions.