• Animal cells and systems
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• 제13권3호
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• pp.283-288
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• 2009

The ubiquitous plasma membrane $Na^+/H^+$ exchanger 1 (NHE1) is rapidly activated in response to various extracellular stimuli and maintains normal cytoplasmic pH. Yeast two-hybrid screening was used in order to identify proteins interacting with NHE1 using its cytoplasmic domain as a bait from HeLa cDNA library. One of the interacting cDNA clones was human Lactate dehydrogenase B (LDHB). In vitro translated LDHB was pulled down together with GST-NHE1.cd protein in the GST pull down assay, confirming the interaction in vitro. LDHB antibody immunoprecipitated endogenous LDHB together with NHE1 from H9c2 cells, validating cellular interaction between NHE1 and LDHB. Subsequent analysis revealed that the overexpression of LDHB increased intracellular PH, implying opening of the NHE1 transporter. Moreover, overexpression of LDHB activated caspase 3 and induced cell death, consistent with the expected phenotype of hyper-activation of NHE1. Collectively, our data indicate that LDHB modulates NHE1 activity via physical interaction.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2805-2809
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• 2013

Objective: This study aimed at investigating whether the orphan nuclear receptor NR4A2 is significantly associated with clinicopathologic features and overall survival of patients with nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was performed to determine NR4A2 protein expression in 84 NPC tissues and 20 non-cancerous nasopharyngeal (NP) tissues. The prognostic significance of NR4A2 protein expression was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results: We did not find a significant association between total NR4A2 expression and clinicopathological variables in 84 patients with NPC. However, we observed that high cytoplasmic expression of NR4A2 was significantly associated with tumor size (T classification) (P = 0.006), lymph node metastasis (N classification) (P = 0.002) and clinical stage (P = 0.017). Patients with higher cytoplasmic NR4A2 expression had a significantly lower survival rate than those with lower cytoplasmic NR4A2 expression (P = 0.004). Multivariate Cox regression analysis analysis suggested that the level of cytoplasmic NR4A2 expression was an independent prognostic indicator for overall survival of patients with NPC (P = 0.033). Conclusions: High cytoplasmic expression of NR4A2 is a potential unfavorable prognostic factor for patients with NPC.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.11.1-11.12
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• 2018

USP15 has been shown to stabilize transcription factors, to be amplified in many cancers and to mediate cancer cell survival. However, the underlying mechanism by which USP15 regulates multiple myeloma (MM) cell proliferation and apoptosis has not been established. Here, our results showed that USP15 mRNA expression was upregulated in MM patients. USP15 silencing induced MM cell proliferation inhibition, apoptosis, and the expression of nuclear and cytoplasmic NF-${\kappa}Bp65$, while USP15 overexpression exhibited an inverse effect. Moreover, in vivo experiments indicated that USP15 silencing inhibited MM tumor growth and NF-${\kappa}Bp65$ expression. PDTC treatment significantly inhibited USP15 overexpression-induced cell proliferation, apoptosis inhibition, and NF-${\kappa}Bp65$ expression. USP15 overexpression promoted NF-${\kappa}Bp65$ expression through inhibition of its ubiquitination, whereas NF-${\kappa}Bp65$ promoted USP15 expression as a positive regulator. Taken together, the USP15-NF-${\kappa}Bp65$ loop is involved in MM tumorigenesis and may be a potential therapeutic target for MM.

• Molecules and Cells
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• 제44권1호
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• pp.13-25
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• 2021

Apoptosis and compensatory proliferation, two intertwined cellular processes essential for both development and adult homeostasis, are often initiated by the mis-regulation of centrosomal proteins, damaged DNA, and defects in mitosis. Fly Anastral spindle 3 (Ana3) is a member of the pericentriolar matrix proteins and known as a key component of centriolar cohesion and basal body formation. We report here that ana3m19 is a suppressor of lethality induced by the overexpression of Sol narae (Sona), a metalloprotease in a disintegrin and metalloprotease with thrombospondin motif (ADAMTS) family. ana3m19 has a nonsense mutation that truncates the highly conserved carboxyl terminal region containing multiple Armadillo repeats. Lethality induced by Sona overexpression was completely rescued by knockdown of Ana3, and the small and malformed wing and hinge phenotype induced by the knockdown of Ana3 was also normalized by Sona overexpression, establishing a mutually positive genetic interaction between ana3 and sona. p35 inhibited apoptosis and rescued the small wing and hinge phenotype induced by knockdown of ana3. Furthermore, overexpression of Ana3 increased the survival rate of irradiated flies and reduced the number of dying cells, demonstrating that Ana3 actively promotes cell survival. Knockdown of Ana3 decreased the levels of both intra- and extracellular Sona in wing discs, while overexpression of Ana3 in S2 cells dramatically increased the levels of both cytoplasmic and exosomal Sona due to the stabilization of Sona in the lysosomal degradation pathway. We propose that one of the main functions of Ana3 is to stabilize Sona for cell survival and proliferation.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.115-115
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• 2017

Zinc finger proteins constitute a large family which has been studied to have various functions in different organisms. Tandem CCCH zinc finger proteins (TZFs), members of the zinc finger protein family, are known to participate as post-transcriptional regulators of gene expression in eukaryotes. Here, we showed that the OsZn15, a gene for tandem CCCH zinc finger protein, is induced by abiotic stress and its overexpression in transgenic rice plants (PGD1:OsZn15) gains higher drought tolerance. Gene expression analysis of promoter:GFP plants revealed that OsZn15 is specifically expressed in anther and embryo, but not in vegetative organs. In-field evaluation, grain yield was higher in the PGD1:OsZn15 than nontransgenic plants under drought conditions. Interestingly, OsZn15 is shown to not only localize at nucleus but also co-localize with both processing bodies (PB) and stress granules (SG), two messenger ribo-nucleoprotein complexes which are known to activate by forming cytoplasmic foci under stress conditions. In sum, these results suggest that OsZn15 increases drought stress tolerance of rice probably by participating in RNA turnover in PB and SG.

• Journal of Gastric Cancer
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• 제17권3호
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• pp.228-236
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• 2017

Purpose: Enolase is a cytoplasmic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the glycolytic pathway. The aim of this study was to investigate whether the overexpression of neuron-specific enolase (NSE) can serve as a prognostic factor in patients with gastric cancer (GC). Materials and Methods: To assess its prognostic value in GC, NSE expression was measured by immunohistochemistry in a clinically annotated tissue microarray comprising of 327 human GC specimens. Cytoplasmic NSE expression was scored from 0 to 4, reflecting the percentage of NSE-positive cells. Results: In terms of histology as per the World Health Organization criteria (P=0.34), there were no differences between the NSE overexpression (NSE-OE) and NSE underexpression (NSE-UE) groups. The NSE-OE group showed a significantly lower rate of advanced GC (P<0.01), lymph node metastasis (P=0.01), advanced stage group (P<0.01), cancer-related death (P<0.01), and cancer recurrence (P<0.01). Additionally, a Kaplan-Meier survival analysis revealed that the NSE-OE group had longer cumulative survival times than the NSE-UE group (log-rank test, P<0.01). However, there were no significant differences in the serum levels of NSE expression in patients with GC and healthy volunteers (P=0.28). Conclusions: Patients with NSE overexpressing GC tissues showed better prognostic results, implying that NSE could be a candidate biomarker of GC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권6호
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• pp.2891-2896
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• 2012

Background: HER2/neu, a member of EGFR family, is over expressed in some tumors. The purpose of this study was to determine the salivary level and tissue expression of HER2/neu in patients with head and neck squamous cell carcinoma (HNSCC) and any correlation with clinicopathologic parameters. Methods: An enzyme-linked immunosorbent assay (ELISA) was used to evaluate the salivary level and immunohistochemistry (IHC) to assess tissue expression of HER2/neu in 28 patients with HNSCC and 25 healthy controls. Results: The salivary levels of HER2/neu in HNSCC patients was not significantly higher than in the healthy controls (p>0.005). There was no apparent correlation in salivary HER2/neu level with clinicopathological features such as age, sex, grade, tumor size and nodal status. All HNSCC specimens were positive (membranous or/and cytoplasmic) for HER2/neu, except one sample. Only one HNSCC specimen was stained in cytoplasm purely. All control specimens were membranous and cytoplasmic positive for HER2/neu. There was a significant difference between cytoplasmic staining in case and control groups (p-value<0.05). Conclusion: In our cases, no overexpression of HER2/neu was observed. Thus, our findings suggested that the use of Her-2 as a salivary marker of HNSCC cannot be recommended.

• Radiation Oncology Journal
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• 제14권2호
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• pp.87-93
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• 1996

목적 : 악성 성상세포종에서 표피 성장 인자 수용체의 과발현의 빈도와 예후 인자로서 가능성을 조사하기 위하여 본 연구를 시행하였다. 대상 및 방법 : 조직학적으로 악성 성상세포종으로 확진되고 방사선 치료를 받은 23명(역형성성상세포종 7예, 다형성 교아세포종 16예)의 파라핀 블록에 antihuman EGFR polyclonal antibody를 이용하여 면역염색을 시행하였다. 결과 : 표피 성장 인자 수용체는 역형성 성상세포종에서는 7예중 2예에서 양성이었고 다형성 교아세포종은 16예중 9예에서 양성으로 양군간의 발현 빈도의 차이는 통계적으로 유의하지 않았다 (p=0.44). 55세 미만의 환자는 11예중 3예에서 양성이었고 55세 이상은 12예중 8예에서 양성이었다(p=0.141). 표피 성장 인자 수용체 음성인 역형성 성상세포종 환자의 평균 생존기간(중앙값)은 37개월이었다. 다형성 교아세포종 환자의 평균 생존 기간은 표피 성장 인자 수용체 음성 군은 중앙값 11개월, 양성 군은 중앙값 7개월이었으나 두 군간의 통계적인 차이는 없었다(p=0.17). 결론 : 55세 이상 연령군에서 표피성장인자 수용체의 과발현의 빈도가 높았다. 다형성 교아세포종 환자의 생존율은 표피성장인자 수용체 과발현에 의하여 감소하였으나 유의한 영향을 받지 않았다.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.243.2-244
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• 2002

Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like and cytoplasmic enzymes. which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Thirty subtypes of PTPs have been identified in human genomes. Among PTPs, PTP1 B has been suggested as a negative regulator of insulin signaling. Overexpression of this enzyme has been known as a cause of obesity and type II diabetes, so it is a target for drug discovery. (omitted)

• International Journal of Industrial Entomology and Biomaterials
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• 제37권2호
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• pp.49-54
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• 2018

To artificially enhance antimicrobial peptide expression in Bombyx mori, we constructed genetically engineered silkworms overexpressing Rel family transcription factor. The truncated BmRelish1 (BmRelish1t) gene contained a Rel homolog domain (RHD), nuclear localization signal (NLS), acidic and hydrophobic amino acid (AHAA)-rich region, and death domain (DD), but no ankyrin-repeat (ANK) domain. The BmRelish1t gene was controlled by B. mori cytoplasmic actin 3 promoter in the PiggyBac transposon vector. Chromosome analysis of G1 generations of a transgenic silkworm with EGFP expression confirmed stable insertion of BmRelish1t. BmRelish1t gene overexpression in transgenic silkworms resulted in higher mRNA expression levels of B. mori antimicrobial peptides such as lebocin(~20.5-fold), moricin(~8.7-fold), and nuecin(~17.4-fold) than those in normal silkworms.