Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locally advanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recent studies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processes and human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR in human CRC cells remain unknown, they were investigated in this study. Materials and Methods: A 5-FU-based concurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profiling of lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines. Results: In total, 2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cells when compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentially expressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-based CRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and their nearby coding genes. Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRC cells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRC patients.
Journal of The Korean Society of Inherited Metabolic disease
/
v.15
no.3
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pp.127-137
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2015
Purpose: The main aim of this study was to compare and analyze expression profiles of microRNAs (miRNAs) to establish miRNA signature of Fabry nephropathy related epithelial mesenchymal transition (EMT). Methods: Expression profiles of miRNAs in kidney tissue samples and cell lines from normal and Fabry disease mouse model were examined by miRNA expression microarray analysis followed by quantitative real-time polymerase chain reaction analysis (qRT-PCR). Results: In the miRNA expression microarray analysis of Fabry mouse kidney tissues compared to wild type mouse, 5 and 3 miRNAs among 1,247 miRNAs examined were up- and down-regulated, respectively. Among them, miR-149-5p was down-regulated about 2-fold in Fabry kidney samples. The down-regulations of miR-149-5p were observed in kidney tissues of under 35 week-old-Fabry mice. However, this down-regulation was not observed in kidney tissues of 42 week-old Fabry mice. In SV40 MES 13 cells, mouse mesangial cells, treated with globotriaosylsphingosine (lyso-Gb3), miR-149-5p was also downregulated. The down-regulation of miR-149-5p induced up-regulation of its target genes related to EMT. Conclusion: The miRNA expression array and qRT-PCR results show that miR-149-5p expression was decreased in kidney tissues of Fabry mice compared to wild type mice under 35 weeks of age. Along with the observation of miR-149-5p expression in Fabry disease cell models, these results indicate that the down-regulated miR-149-5p were related to the biological response of mesangial cells to lyso-Gb3 and also have influence to the transcriptional up-regulation of its target genes. These results suggest miR-149-5p might play important roles in the Fabry nephropathy.
Owing to the risk of fetal loss associated with prenatal diagnostic procedures (amniocentesis, chorionic villus sampling), noninvasive prenatal diagnosis (NIPD) is ultimate goal of prenatal diagnosis. The discovery of circulating cell-free fetal DNA (cffDNA) in maternal plasma in 1997 has opened up new probabilities for NIPD by Dr. Lo et al. The last decade has seen great development in NIPD. Fetal sex and fetal RhD status determination by cffDNA analysis is already in clinical use in certain countries. For routine use, this test is limited by the amount of cell-free maternal DNA in blood sample, the lack of universal fetal markers, and appropriate reference materials. To improve the accuracy of detection of fetal specific sequences in maternal plasma, internal positive controls to confirm to presence of fetal DNA should be analyzed. We have developed strategies for noninvasive determination of fetal gender, and fetal RhD genotyping using cffDNA in maternal plasma, using real-time quantitative polymerase chain reaction (RT-PCR) including RASSF1A epigenetic fetal DNA marker (gender-independent) as internal positive controls, which is to be first successful study of this kind in Korea. In our study, accurate detection of fetal gender through gestational age, and fetal RhD genotyping in RhD-negative pregnant women was achieved. In this assay, we show that the assay is sensitive, easy, fast, and reliable. These developments improve the reliability of the applications of circulating fetal DNA when used in clinical practice to manage sex-linked disorders (e.g., hemophilia, Duchenne muscular dystrophy), congenital adrenal hyperplasia (CAH), RhD incompatibility, and the other noninvasive pregnant diagnostic tests on the coming soon. The study was the first successful case in Korea using cffDNA in maternal plasma, which has created a new avenue for clinical applications of NIPD.
The present study aimed to investigate the effects of lycopene on hepatic metabolic- and immune-related gene expression in laying hens. A total of 48 25-week-old White Leghorn hens were randomly allocated into four groups consisting of four replicates of three birds: control (basal diet), T1 (basal diet + 10 mg/kg of tomato powder-containing lycopene), T2 (basal diet + 10 mg/kg of micelles of tomato powder-containing lycopene), and T3 (basal diet + 10 mg/kg of purified lycopene). Chickens were fed ad libitum for 5 weeks, and then total RNA was extracted from the livers for quantitative RT-PCR analysis. Peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$) expression was decreased in the liver of chickens after lycopene supplementation (P<0.05). Micellar lycopene supplementation decreased the expression of PPAR${\gamma}$ target genes including fatty acid binding protein 4 (FABP4) and fatty acids synthase (FASN) in the T2 group (P<0.05). Sterol regulatory element-binding protein 2 (SREBP2) and C/EBP-${\alpha}$ were also downregulated in hens fed with micellar lycopene (P<0.05). Glucose transporter 8 (GLUT-8) was upregulated in the T2 and T3 groups (P<0.05). However, the expression of carnitine palmitoyltransferase 1 (CPT-1) was not changed by lycopene supplementation. Pro-inflammatory cytokines such as tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and interleukin 6 (IL-6) were downregulated by lycopene supplementation (P<0.05). These data suggest that the type of lycopene supplementation is critical and that micelles of tomato powder-containing lycopene may play an important role in the modulation of lipid metabolism and immunity in chickens.
Placenta-derived mesenchymal stem cells (PD-MSCs) are promising candidates for cell-based therapy in regenerative medicine. The migration and homing potential of PD-MSCs to injured sites is a critical property of MSC engraftment. MicroRNAs (miRNAs) have recently been shown to regulate the critical functions of MSCs, such as proliferation, survival, and migration. The objective of the present study was to identify the miRNA and target genes involved in PD-MSCs homing in a bile duct ligation (BDL) rat model. We selected candidate miRNAs targeting genes for PD-MSCs homing based on microarray analysis. PD-MSC engraftment in BDL-injured rat liver was identified by immunofluorescence assay and human-specific Alu gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) one week after transplantation. Compared with migrated naïve PD-MSCs under hypoxic and normoxic conditions (Hyp/Nor), the transplanted group with PD-MSCs (Tx) showed distinct differences in miRNA expressions in BDL-injured rat liver. We also validated the miRNAs and their target genes for PD-MSCs homing. The expressions of integrin α4 (ITGA4) and integrin α5 (ITGA5) target genes for miR-199a-5p and miR-148a-3p were significantly upregulated in the Tx group (p<0.05). In addition, integrin β1 (ITGB1) and integrin β8 (ITGB8) were upregulated by suppressing miR-183-5p and miR-145-5p, respectively. These results demonstrated that PD-MSCs regulate miRNA expression related to the integrin family for their homing effects on the BDL-injured rat liver. The findings further suggest that miRNA-mediated regulation of the integrin family contributes to the therapeutic efficacy of PD-MSCs in the rat hepatic fibrosis model by BDL.
Ji-Hye Hong;Young Duck Choi;Gye Won Lee;Young Ho Cho
Journal of Life Science
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v.33
no.11
/
pp.905-914
/
2023
To evaluate the effectiveness of the skin barrier improvement of lactic acid (LA) and gluconolactone (GL), the expression of filaggrin, loricrin, hyaluronic acid (HA), hyaluronan syhthase-2 (HAS2), and aquaporine-3 (AQP3) in keratinocytes, and the moisture content and transepidermal water loss (TEWL) by clinical trials were evaluated. The expression levels of filaggrin and locricrin, which are the main factors affecting the proper functioning of skin barrier function, and HA, HAS2, and AQP3, which are skin moisturizing-related proteins measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The results showed that the expression levels of the factors that decreased by H2O2 treatment were significantly increased by LA, GL, and a mixture of LA and GL at the mRNA and protein levels (p<0.05). The nanoemulsion containing a mixture of LA and GL was prepared using the emulsion inversion method, and the average particle size was 299.9 ± 0.287 nm. After measuring the TEWL of nanoemulsion using Vapometer, it was found that TEWL significantly decreased by 15.53% and 26.73% after two weeks and four weeks of product use, respectively, compared to TEWL before product use (p<0.001). Similarly, the skin moisture content of the nanoemulsion significantly increased by 15.40% and 26.59% after two weeks and four weeks of product use, respectively, compared to skin moisture content before product use (p<0.001). Therefore, the skin barrier function and moisturizing effect of a mixture of LA and GL are shown by increasing the moisture content and decreasing the TEWL by increasing the expression of filaggrin, loricrin, HA, HAS2, and AQP3. This suggests the possibility for the development of functional cosmetic ingredients in the future.
Background: ${\beta}$-elemene, extracted from herb medicine Curcuma wenyujin has potent anti-tumor effects in various cancer cell lines. However, the activity of ${\beta}$-elemene against glioma cells remains unclear. In the present study, we assessed effects of ${\beta}$-elemene on human glioma cells and explored the underlying mechanism. Materials and Methods: Human glioma U87 cells were used. Cell proliferation was determined with MTT assay and colony formation assay to detect the effect of ${\beta}$-elemene at different doses and times. Fluorescence microscopy was used to observe cell apoptosis with Hoechst 33258 staining and change of glioma apoptosis and cell cycling were analyzed by flow cytometry. Real-time quantitative PCR and Western-blotting assay were performed to investigated the influence of ${\beta}$-elemene on expression levels of Fas/FasL, caspase-3, Bcl-2 and Bax. The experiment was divided into two groups: the blank control group and ${\beta}$-elemne treatment group. Results: With increase in the concentration of ${\beta}$-elemene, cytotoxic effects were enhanced in the glioma cell line and the concentration of inhibited cell viability ($IC_{50}$) was $48.5{\mu}g/mL$ for 24h. ${\beta}$-elemene could induce cell cycle arrest in the G0/G1 phase. With Hoechst 33258 staining, apoptotic nuclear morphological changes were observed. Activation of caspase-3,-8 and -9 was increased and the pro-apoptotic factors Fas/FasL and Bax were upregulated, while the anti-apoptotic Bcl-2 was downregulated after treatment with ${\beta}$-elemene at both mRNA and protein levels. Furthermore, proliferation and colony formation by U87 cells were inhibited by ${\beta}$-elemene in a time and does-dependent manner. Conclusions: Our results indicate that ${\beta}$-elemene inhibits growth and induces apoptosis of human glioma cells in vitro. The induction of apoptosis appears to be related with the upregulation of Fas/FasL and Bax, activation of caspase-3,-8 and -9 and downregulation of Bcl-2, which then trigger major apoptotic cascades.
Objective: This study was performed to compare the expression of osteopontin (OPN) mRNA and protein in the eutopic and ectopic endometrial tissues in women with endometriosis and endometrial tissues in women without endometriosis. Methods: A total of 32 women with histologically confirmed endometriosis were recruited for study group. For controls, 34 women undergoing operative treatment for cervical intraepithelial neoplasia (CIN) or benign gynecologic condition other than endometriosis were recruited. At the time of laparoscopy or laparotomy, a biopsy specimen was taken from the endometrial cavity and peritoneal endometrial implant or endometrioma whenever appropriate. We employed real time quantitative RT-PCR to quantify OPN mRNA expression of these tissues and performed western blot analysis to measure the quantity of OPN. Results: The expression of OPN mRNA was significantly higher in both eutopic and ectopic endometrial tissues of women with endometriosis than in endometrial tissues of controls during both proliferative and secretory phase. In the eutopic endometrial tissue of women with endometriosis, OPN mRNA expression significantly increased during the secretory phase compared to the proliferative phase in women with endometriosis as well as controls. However, in the ectopic endometrial tissue, OPN mRNA expression significantly decreased during the secretory phase compared to the proliferative phase. The expression of OPN protein was significantly higher in women with endometriosis than in controls. Conclusion: This study shows the marked expression of OPN mRNA and protein in eutopic and ectopic endometrial tissues in women with endometriosis may be associated with the adhesion and invasion of endometrial explants.
The uterus plays a critical role in pregnancy and steroid hormones, and both estrogen (E2) and progesterone (P4) especially play important roles in the cross-talk between embryos and uterus to support the pregnancy. E2 stimulates uterine growth during early pregnancy to prepare for implantation of embryos. This cross-talk during the implantation period involves hormones (E2 and P4) and growth factors, including insulin-like growth factor-I (IGF-I). In the uterus of a pregnant pig, the action of E2 is mediated by estrogen receptor-${\beta}$ (ER-${\beta}$). The expression of ER-a was much higher in early pregnancy than in mid- and late- pregnancy, suggesting E2 secretion from embryos enhances transcription of ER-a during early pregnancy. In order to prove whether IGF-I is an E2 target gene, quantitative real-time PCR was performed on ovariectomized murine uterus with E2 and/or P4 treatment(s). Increased IGF-I mRNA expression was observed with E2 treatment, however, it was not significantly induced by P4 treatment, which clearly demonstrates that, in mice, E2 depends on the activation of uterine IGF-I gene expression. The expression of IGF-I in the uterus of pigs was much higher in early pregnancy than in mid- and late- pregnancy and these data exhibited the same expression pattern with the ER-${\beta}$ gene expression in the uterus. It suggests that a positive co-relationship between IGF-I and ER-${\beta}$ expression exists in the uterus, and that both gene expressions of IGF-I and ER-${\beta}$ are regulated by E2. It further suggests that uterine the IGF-I gene expression might be initiated by E2 secreted from embryos to increase ER-${\beta}$ gene expression, and that this increased ER-${\beta}$ further stimulates the expression of IGF-I in the uterus during early pregnancy.
Human mesenchymal stem cells (hMSCs) in bone marrow (BM) can be induced to differentiate into a variety of mesenchymal tissues, including adipocytes, osteoblasts and chondroblasts, under the influence of certain growth or environmental factors. In this study, we analyzed the differentiation process and the associated gene expression profiles inherent to the process by which hMSCs differentiate into osteoblasts. We conducted a comparison of gene expression profiles of the normal human BM MSCs, using human 8K cDNA microarray, incubated in media containing either a combination of $\beta$-glycerol phosphate, L-ascorbic acid, and dexamethasone, or in medium lacking these osteogenic supplements. During the osteoblastic differentiation process, 36 genes were determined to be up-regulated, and 59 genes were shown to be down-regulated. Osteoprotegerin, LRP5, and metallothionein 2A, all of which are associated with the osteogenetic process, were up-regulated, and genes associated with the differentiation of MSCs into other lineages, including muscle, adipose tissue and vascular structure were down-regulated. The set of differentially expressed genes reported in this work should contribute to our current understanding of the processes inherent to the differentiation of MSCs into osteoblasts.
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