• 제목/요약/키워드: Gene Expression Analysis

검색결과 3,388건 처리시간 0.034초

Prognostic Significance of Hes-1, a Downstream Target of Notch Signaling in Hepatocellular Carcinoma

  • Zou, Jing-Huai;Xue, Tong-Chun;Sun, Chun;Li, Yan;Liu, Bin-Bin;Sun, Rui-Xia;Chen, Jie;Ren, Zheng-Gang;Ye, Sheng-Long
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권9호
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    • pp.3811-3816
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    • 2015
  • Background: Hairy and enhancer of split 1 (Hes-1) protein is a downstream target of Notch signaling and is a basic helix-loop-helix transcriptional repressor. However, definitive evidence for a role in hepatocellular carcinoma (HCC) cells has not been reported. Here, Hes-1 was revealed to an important component of the Notch signaling cascade in HCC cell lines possessing different potential for lung metastasis. Materials and Methods: RNAi mediated by plasmid constructs was used to analyze the role of Hes-1 in MHCC-97L HCC cells by assessing proliferation, apoptosis, cell migration and matrigel invasion following transfection. Hes-1 protein expression analysis in HCC tissue was also conducted by immunohistochemistry. Results: Our studies revealed that Hes-1 was decreased in HCC cell lines with higher lung metastasis potential at both the mRNA and protein levels. Down-regulation of the Hes-1 gene in MHCC-97L cells resulted in increased cell proliferation, reduced apoptosis and increased migration and invasion. Conclusions: Hes-1 has potential prognostic value in post-surgical HCC patients and may be an independent prognostic indicator for overall survival and tumor recurrence. These findings have important implications for understanding the mechanisms by which Hes-1 participates in tumor proliferation and invasion.

PU.1 Is Identified as a Novel Metastasis Suppressor in Hepatocellular Carcinoma Regulating the miR-615-5p/IGF2 Axis

  • Song, Li-Jie;Zhang, Wei-Jie;Chang, Zhi-Wei;Pan, Yan-Feng;Zong, Hong;Fan, Qing-Xia;Wang, Liu-Xing
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권9호
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    • pp.3667-3671
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    • 2015
  • Invasion and metastasis is the major cause of tumor recurrence, difficulty for cure and low survival rate. Excavating key transcription factors, which can regulate tumor invasion and metastasis, are crucial to the development of therapeutic strategies for cancers. PU.1 is a master hematopoietic transcription factor and a vital regulator in life. Here, we report that, compared to adjacent non-cancerous tissues, expression of PU.1 mRNA in metastatic hepatocellular carcinoma (HCC), but not primary HCC, was significantly down-regulated. In addition, levels of PU.1 mRNA in metastatic hepatoma cell lines MHCC97L and MHCC97H were much lower than in non-metastatic Hep3B cells. Transwell invasion assays after PU.1 siRNA transfection showed that the invasion of hepatoma cell lines was increased markedly by PU.1 knockdown. Oppositely, overexpression of PU.1 suppressed the invasion of these cells. However, knockdown and overexpression of PU.1 did not influence proliferation. Finally, we tried to explore the potential mechanism of PU.1 suppressing hepatoma cell invasion. ChIP-qPCR analysis showed that PU.1 exhibited a high binding capacity with miR-615-5p promoter sequence. Overexpression of PU.1 caused a dramatic increase of pri-, pre- and mature miR-615-5p, as well as a marked decrease of miR-615-5p target gene IGF2. These data indicate that PU.1 inhibits invasion of human HCC through promoting miR-615-5p and suppressing IGF2. These findings improve our understanding of PU.1 regulatory roles and provided a potential target for metastatic HCC diagnosis and therapy.

Research article Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation and myotube growth

  • Lee, Soo-Yeon;Go, Ga-Yeon;Vuong, Tuan Anh;Kim, Jee Won;Lee, Sullim;Jo, Ayoung;An, Jun Min;Kim, Su-Nam;Seo, Dong-Wan;Kim, Jin-Seok;Kim, Yong Kee;Kang, Jong-Sun;Lee, Sang-Jin;Bae, Gyu-Un
    • Journal of Ginseng Research
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    • 제42권1호
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    • pp.116-121
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    • 2018
  • Background: Black ginseng (BG) has greatly enhanced pharmacological activities relative to white or red ginseng. However, the effect and molecular mechanism of BG on muscle growth has not yet been examined. In this study, we investigated whether BG could regulate myoblast differentiation and myotube hypertrophy. Methods: BG-treated C2C12 myoblasts were differentiated, followed by immunoblotting for myogenic regulators, immunostaining for a muscle marker, myosin heavy chain or immunoprecipitation analysis for myogenic transcription factors. Results: BG treatment of C2C12 cells resulted in the activation of Akt, thereby enhancing hetero-dimerization of MyoD and E proteins, which in turn promoted muscle-specific gene expression and myoblast differentiation. BG-treated myoblasts formed larger multinucleated myotubes with increased diameter and thickness, accompanied by enhanced Akt/mTOR/p70S6K activation. Furthermore, the BG treatment of human rhabdomyosarcoma cells restored myogenic differentiation. Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

Kunitz Trypsin Inhibitor 발현 억제에 의한 콩 뿌리혹 수의 감소 (Inhibition of SKTI Synthesis in Agrobacterium rhizogenes-induced Hairy Root Reduces the Number of Nodule in Soybean)

  • 김선형;임채우;박지영;황철호
    • 한국작물학회지
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    • 제54권3호
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    • pp.299-306
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    • 2009
  • 콩과식물의 뿌리혹 형성을 조절하는 신호물질의 확인을 위해 신팔달콩2호의 줄기 수액 단백질 중에서 B. japonicum USDA110의 접종 후 2.5일(DAI)에 20 kDa의 SKTI 단백질이 증가하였다가 7 DAI에는 감소되면서 6 kDa의 작은 크기의 단백질이 증가되었다. 이러한 단백질의 차등발현은 조사한 3종의 콩에서 모두 유사하게 나타났으며 특히 대원콩에서 가장 두드러졌다. Western 분석으로 7 DAI에서 증가하는 6 kDa 단백질이 SKTI 항체와 특이적 반응을 하는 것으로 확인하여 SKTI가 절단되어 생긴 펩타이드로 추정되었다. 이러한 결과를 통해 20 KDa의 SKTI단백질이 콩의 뿌리혹 착생 초기단계인 2.5 DAI에 영향을 주고, 7 DAI로 진행되면서 6 kDa의 작은 크기의 단백질로 분해되어 그 양이 감소하는 것으로 생각된다. RNAi를 이용하여 유전자 기능이 억제된 형질전환된 모상근의 뿌리혹을 실제 형질전환이 확인된 모상근에 착생된 뿌리혹의 수를 비교한 결과 비재조합 A. rhizogenes을 접종시킨 대조구에 비해 SKTI RNAi 유전자를 형질전환한 모상근에서 모상근 당 착생된 뿌리혹 수가 감소되었다. 실시간 PCR 방법으로 형질전환된 모상근의 SKTI 전사체 수준에서도 상응하는 차이를 확인하였다. 이에 정확한 기작을 알 수 없지만 SKTI유전자가 뿌리혹 형성 초기에 뿌리혹 형성과정에 직간접적으로 관련하고 있음을 확인하였다. Sesbania rostrata의 뿌리혹 발생과정의 Protease 저해제와 같이 뿌리 혹 내의 감염세포 대 비감염세포의 비율을 조절하는 SKTI 발현 억제는 이러한 균형을 교란하여 뿌리혹의 생성을 억제하는 것으로 추정된다.

반하후박탕(半夏厚朴湯)이 생쥐의 심리적 스트레스에 미치는 영향과 유전자 분석 (Effect of Banhahoobak-tang (Banxiahoupo-tang) Extract (BHTe) on Psychological Stress)

  • 최금애;조수인;김경수;최창원;위통순;양승정;박수연;김경옥
    • 동의신경정신과학회지
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    • 제26권2호
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    • pp.117-130
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    • 2015
  • Objectives: Banhahoobak-tang has been used to treat plum-pit qi, chest and hypochondriac distension, moist or greasy tongue coat, and wiry slow or wiry slippery pulse. It might be used to control coughing and vomiting. We observed that Banhahoobak-tang extract (BHTe) had anti-psychological stress effect. The objective of this study was to determine the effect of BHTe on restoring the transcriptional regulation of genes related to psychological stress. Methods: After giving psychological stress to mice, BHTe was orally administered at 100 mg/kg/day for five days. After extracting whole brain tissue from the mice, the gene expression changes were determined by microarray. Transcription factor binding site (TFBS) analysis showed up- and down-regulated genes related to psychological stress were protected by BHTe and segregated according to the structure of TFBS. We performed text based Pubmed search to select significant target genes involved in psychological stress affected by BHTe. Results: 1. Serum corticosterone level was decreased in the BHTe administered group, although the psychological stress was increased. 2. The BHTe administered group had no significant change in noradrenaline content in brain tissue, but the psychological stress group had decreased level. 3. The BHTe administered group had increased time of staying at open-arm than the psychological stress group. 4. Microarray revealed that TANK and RARA genes were up-regulated genes while AES, CDC42, FOS, NCL, and PVR were down-regulated genes by psychological stress but restored by BHTe.

Studies on Manifestation of Hybrid Vigour in $F_1$ and Three-Way Crosses of Multivoltine $\times$ Bivoltine Silkworm, Bombyx mori L.

  • Rao, D.Raghavendra;Banerjee, Sharmista;Kariappa, B.K.;Singh, Ravindra;Premalatha, V.;Dandin, S.B.
    • International Journal of Industrial Entomology and Biomaterials
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    • 제7권2호
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    • pp.209-219
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    • 2003
  • An experiment was initiated to evaluate hybrid vigour in twelve F$_1$ hybrids and seven three-way crosses of multivoltine ${\times}$ bivoltine silkworm between newly evolved multivoltine breed BL67 with productive bivoltine CSR breeds and hybrids. Analysis of variances computed for different characters among F$_1$hybrids and three-way crosses showed highly significant differences among them indicating presence of both additive and non-additive gene actions for the expression of these characters. Among twelve F$_1$ hybrids, two F$_1$ hybrids viz., BL67${\times}$CSR$_4$and BL67${\times}$CSR$_{5}$ have expressed significant heterosis for nine characters and two hybrids viz., BL67${\times}$NB$_4$D$_2$and PM${\times}$NB$_4$D$_2$ for eight characters whereas out of nine three-way crosses, three hybrids viz., BL67${\times}$ (CSR$_3$${\times}$CSR$_{6}$), BL67${\times}$(CSR$_{16}$${\times}$CRS$_{17}$) and BL67${\times}$(CSR$_{18}$ ${\times}$CSR$_{19}$) expressed significant heterosis for eight characters. In the present study, it is observed that the cocoons of two hybrids viz., BL67${\times}$CSR$_4$and BL67${\times}$CSR$_{19}$ were found to be uniform as these hybrids showed lowest CV% (5.35 and 5.38) among twelve F$_1$ hybrids and seven three way crosses between multivoltine ${\times}$ bivoltine hybrids. Four F$_1$ hybrids viz., BL67${\times}$CSR$_4$, BL67${\times}$CSR$_{5}$, BL67${\times}$ (CSR$_3$${\times}$CSR$_{6}$), BL67${\times}$(CSR$_{16}$${\times}$CRS$_{17}$) and BL67${\times}$(CSR$_{18}$ ${\times}$CSR$_{19}$) showed superiority in expressing hybrid vigour and are considered as best heterotic hybrids for commercial exploitation.ion.ation.ion.ation.ion.

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

  • Farahani, Roya Kishani;Azimzadeh, Pedram;Rostami, Elham;Malekpour, Habib;Aghdae, Hamid Asadzadeh;Pourhoseingholi, Mohamad Amin;Mojarad, Ehsan Nazemalhosseini;Zali, Mohammad Reza
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권10호
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    • pp.4215-4218
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    • 2015
  • Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

A novel PRF1 gene mutation in a fatal neonate case with type 2 familial hemophagocytic lymphohistiocytosis

  • Kim, Jae Yeon;Shin, Jeong Hee;Sung, Se In;Kim, Jin Kyu;Jung, Ji Mi;Ahn, So Yoon;Kim, Eun Sun;Seo, Ja-Young;Kang, Eun-Sook;Kim, Sun-Hee;Kim, Hee-Jin;Chang, Yun Sil;Park, Won Soon
    • Clinical and Experimental Pediatrics
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    • 제57권1호
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    • pp.50-53
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    • 2014
  • Hemophagocytic lymphohistiocytosis (HLH) occurs in the primary form (genetic or familial) or secondary form (acquired). The familial form of HLH (FHL) is a potentially fatal autosomal recessive disorder that occurs because of constitutional defects in cell-mediated cytotoxicity. Here, we report a fatal neonatal case of type 2 FHL (FHL2) that involved a novel frameshift mutation. Clinically, the newborn presented with severe sepsis-like features and required mechanical ventilation and continuous venovenous hemodiafiltration. Flow cytometry analysis showed marked HLH and complete absence of intracytoplasmic perforin expression in cytotoxic cells; therefore, we performed molecular genetic analyses for PRF1 mutations, which showed that the patient had a compound heterozygous mutation in PRF1, that is, c.65delC ($p.Pro22Argfs^*2$) and c.1090_1091delCT ($p.Leu364Glufs^*93$). Clinical and genetic assessments for FHL are required for neonates with refractory fever and progressive multiple organ failure, particularly when there is no evidence of microbiological or metabolic cause.

Neural Growth Factor Stimulates Proliferation of Spinal Cord Derived-Neural Precursor/Stem Cells

  • Han, Youngmin;Kim, Kyoung-Tae
    • Journal of Korean Neurosurgical Society
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    • 제59권5호
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    • pp.437-441
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    • 2016
  • Objective : Recently, regenerative therapies have been used in clinical trials (heart, cartilage, skeletal). We don't make use of these treatments to spinal cord injury (SCI) patients yet, but regenerative therapies are rising interest in recent study about SCI. Neural precursor/stem cell (NPSC) proliferation is a significant event in functional recovery of the central nervous system (CNS). However, brain NPSCs and spinal cord NPSCs (SC-NPSCs) have many differences including gene expression and proliferation. The purpose of this study was to investigate the influence of neural growth factor (NGF) on the proliferation of SC-NPSCs. Methods : NPSCs ($2{\times}10^4$) were suspended in $100{\mu}L$ of neurobasal medium containing NGF-7S (Sigma-Aldrich) and cultured in a 96-well plate for 12 days. NPSC proliferation was analyzed five times for either concentration of NGF (0.02 and 2 ng/mL). Sixteen rats after SCI were randomly allocated into two groups. In group 1 (SCI-vehicle group, n=8), animals received 1.0 mL of the saline vehicle solution. In group 2 (SCI-NGF group, n=8), the animals received single doses of NGF (Sigma-Aldrich). A dose of 0.02 ng/mL of NGF or normal saline as a vehicle control was intra-thecally injected daily at 24 hour intervals for 7 days. For Immunohistochemistry analysis, rats were sacrificed after one week and the spinal cords were obtained. Results : The elevation of cell proliferation with 0.02 ng/mL NGF was significant (p<0.05) but was not significant for 2 ng/mL NGF. The optical density was increased in the NGF 0.02 ng/mL group compared to the control group and NGF 2 ng/mL groups. The density of nestin in the SCI-NGF group was significantly increased over the SCI-vehicle group (p<0.05). High power microscopy revealed that the density of nestin in the SCI-NGF group was significantly increased over the SCI-vehicle group. Conclusion : SC-NPSC proliferation is an important pathway in the functional recovery of SCI. NGF enhances SC-NPSC proliferation in vitro and in vivo. NGF may be a useful option for treatment of SCI patients pending further studies to verify the clinical applicability.

오미자 활성성분 DDB의 NF-${\kappa}B$ 신호 전달 및 염증물질 발현 조절 (Regulation of Inflammatory Repertoires and NF-${\kappa}B$ Signal Transduction by DDB, an Active Compound from Schizandra Chinensis Baillon)

  • 주성수;유영민;원태준;김민정;이선구;황광우;이도익
    • IMMUNE NETWORK
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    • 제6권1호
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    • pp.27-32
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    • 2006
  • Background: Chronic inflammation in the brain has known to be associated with the development of a various neurological diseases including dementia. In general, the characteristic of neuro-inflammation is the activated microglia over the brain where the pathogenesis occurs. Pro-inflammatory repertoires, interleukin-1${\beta}$ (IL-1${\beta}$) and nitric oxide (NO), are the main causes of neuro-degenerative disease, particularly in Alzheimer's disease (AD) which is caused by neuronal destruction. Those pro-inflammatory repertoires may lead the brain to chronic inflammatory status, and thus we hypothesized that chronic inflammation would be inhibited when pro-inflammatory repertoires are to be well controlled by inactivating the signal transduction associated with inflammation. Methods: In the present study, we examined whether biphenyl dimethyl dicarboxylate (DDB), an active compound from Schizandra chinensis Baillon, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS) and IL-1${\beta}$. Western blots were also used for the analysis of NF-${\kappa}B$ and I${\kappa}B$. Results: In the study, we found that DDB effectively inhibited IL-1${\beta}$ as well as NO production in BV-2 microglial cell, and the translocation of NF-${\kappa}B$ was comparably inhibited in the presence of DDB comparing those to the positive control, lipopolysaccharide. Conclusion: The data suggested that the DDB from Schizandra chinensis Baillon may play an effective role in inhibiting the pro-inflammatory repertoires which may cause neurodegeneration and the results imply that the compound suppresses a cue signal of the microglial activation which can induce the brain pathogenesis such as Alzheimer's disease.