• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.897-902
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• 2015

PTEN (phosphatase and tensin homologue), as a tumor suppressor gene, plays a significant role in regulating cell growth, proliferation, and apoptosis. Results from published studies for association between the PTEN IVS4 I/D (rs3830675) polymorphism and cancer risk are inconsistent and inconclusive. We therefore conducted a meta-analysis to evaluate the potential association between PTEN IVS4 I/D polymorphism and risk of cancer in detail. We searched PubMed (Medline) and EMBASE web databases to cover all relevant studies published until December 2013. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95%CIs) were used to appraise the strength of association. A total of 1,993 confirmed cancer cases and 3,200 controls were included from six eligible case-control studies. Results from overall pooled analysis suggested a significant effect of the PTEN IVS4 I/D polymorphism and cancer risk in all genetic models, i.e., allele (I vs D: OR=0.743, 95%CI=0.648 to 0.852, p=0.001), homozygous (II vs DD: OR=0.673, 95%CI=0.555 to 0.816, p=0.001), heterozygous (ID vs DD: OR=0.641, 95%CI=0.489 to 0.840, p=0.001), dominant (II+ID vs DD: OR=0.626, 95%CI=0.489 to 0.802, p=0.001) and recessive (II vs DD+ID: OR=0.749, 95%CI=0.631 to 0.889, p=0.001). Significant publication bias was detected during the analysis. The present meta-analysis suggests that the PTEN IVS4 I/D polymorphism is significantly associated with reduced risk of cancer. However, future larger studies with other groups of populations are warranted to clarify this association.

• Asian Pacific Journal of Cancer Prevention
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• 제14권2호
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• pp.1067-1072
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• 2013

Hiwi, a human homologue of the Piwi family, plays an important role in stem cell self-renewal and is overexpressed in various human tumors. This study aimed to determine whether an RNA interference-based strategy to suppress Hiwi expression could inhibit tumor growth in a xenograft mouse model. A rare population of $SSC^{lo}\;Alde^{br}$ cells was isolated and identified as lung cancer stem cells in our previous study. Plasmids containing U6 promoter-driven shRNAs against Hiwi or control plasmids were successfully established. The xenograft tumor model was generated by subcutaneously inoculating with lung cancer stem cell $SSC^{lo}\;Alde^{br}$ cells. After the tumor size reached about 8 mm in diameter, shRNA plasmids were injected into the mice via the tail vein three times a week for two weeks, then xenograft tumor growth was assessed. In nude mice, intravenously delivery of Hiwi shRNA plasmids significantly inhibited tumor growth compared to treatment with control scrambled shRNA plasmids or the vehicle PBS. No mice died during the experiment and no adverse events were observed in mice administered the plasmids. Moreover, delivery of Hiwi shRNA plasmids resulted in a significant suppressed expression of Hiwi and ALDH-1 in xenograft tumor samples, based on immunohistochemical analysis. Thus, shRNA-mediated Hiwi gene silencing in lung cancer stem cells by an effective in vivo gene delivery strategy appeared to be an effective therapeutic approach for lung cancer, and may provide some useful clues for RNAi gene therapy in solid cancers.

• BMB Reports
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• 제41권9호
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• pp.664-669
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• 2008

Znf230, the mouse homologue of the human spermatogenesis-related gene, ZNF230, has been cloned by rapid amplification of cDNA ends (RACE). This gene is expressed predominantly in testis, but its expression in different testicular cells and spermatogenic stages has not been previously analyzed in detail. In the present study, the cellular localization of the Znf230 protein in mouse testis and epididymal spermatozoa was determined by RT-PCR, immunoblotting, immunohistochemistry and immunofluorescence. It is primarily expressed in the nuclei of spermatogonia and subsequently in the acrosome system and the entire tail of developing spermatids and spermatozoa. The results indicate that Znf230 may play an important role in mouse spermatogenesis, including spermatogenic cell proliferation and sperm maturation, as well as motility and fertilization.

• 미생물학회지
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• 제46권4호
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• pp.401-404
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• 2010

출아효모 Saccharomyces cerevisiae에서 RNA-binding 단백질인 Tho1은 mRNA가 전사되는 동안 초기 mRNA에 결합하여 mRNP 생성과 성숙한 mRNA의 핵에서 세포질로의 방출에 관여하는 것으로 여겨진다. 분열효모 Schizosaccharomyces pombe에서도 Tho1과 유사한 단백질을 암호화하는 유전자(spTho1로 명명)를 찾아 그 특성을 조사하였다. 이배체 S.pombe 균주에 하나의 spTho1 유전자만을 결실시킨 후 4분체분석을 수행한 결과, 이 유전자는 생장에 반드시 필요하지 않았다. 또한 spTho1 결실 돌연변이는 mRNA의 핵에서 세포질로의 방출도 정상적으로 보였다. 그러나 티아민에 의해 발현이 조절되는 강력한 프로모터를 이용하여 spTho1를 과발현시키면, 세포의 생장이 억제되었으며 $poly(A)^+$ RNA가 핵 안에 축적되었다. 이와 같은 결과들은 spTho1 유전자가 필수적이지는 않지만 mRNA의 핵에서 세포질로의 방출에 관여하고 있음을 시사한다.

• Molecular & Cellular Toxicology
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• 제4권4호
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• pp.307-310
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• 2008

AAD16034 is an alginate lyase from Pseudoalteromonas sp. IAM14594. A very close homologue with known 3D structure exists (marine bacterium Pseudoalteromonas sp. strain no. 272). A three-dimensional structure of AAD16034 was generated based on this template (PDB code: 1J1T) by comparative modeling. The modeled enzyme exhibited a jelly-roll like structure very similar to its template structure. Both enzymes possess the characteristic alginate sequence YFKhG+Y-Q. Since AAD16034 displays enzymatic activity for poly-M alginate, docking of a tri-mannuronate into the modeled structure was performed. Two separate and adjacent binding sites were found. The ligand was accommodated inside each binding site. By considering both binding sites, a plausible binding pose for the poly-M alginate polymer could be deduced. From the modeled docking pose (i.e., the most important factor that attracts alginate polymer into this lyase) the most likely interaction was electrostatic. In accordance with a previous report, the hydroxyl group of Y345 was positioned close to the ${\alpha}$-hydrogen of ${\beta}$-mannuronate, which was suitable to initiate a ${\beta}$-elimination reaction. K347 was also very near to the carboxylatemoiety of the ligand, which might stabilize the dianion intermediate during the ${\beta}$-elimination reaction. This implies that the characteristic alginate sequence is absolutely crucial for the catalysis. These results may be exploited in the design of novel enzymes with desired properties.

• Animal cells and systems
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• 제13권4호
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• pp.399-403
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• 2009

$p19^{ras}$ is an alternative splicing variant of the proto-oncogene c-H-ras pre-mRNA of $p21^{ras}$. In contrast to $p21^{ras}$, $p19^{ras}$ does not have a C-terminal CAAX motif that targets the plasma membrane and is localized to both the cytoplasm and nucleus. We found that $p19^{ras}$ activated the transcriptional activity of $p73{\beta}$ through protein-protein interactions in the nucleus. p73 is known to play an important role in cellular damage responses such as apoptosis. Although p73 is a structural and functional homologue of p53, p73-mediated apoptosis has not yet been clearly elucidated. In this study, we demonstrate that the interaction between $p19^{ras}$ and $p73{\beta}$ accelerated $p73{\beta}$-induced apoptosis through a caspase-3 dependent pathway. Treatment with DEVD-CHO, a caspase inhibitor, also strengthened $p73{\beta}$-mediated apoptosis through a caspase-3 dependent pathway. Furthermore, the enhanced transcriptional activity of endogenous $p73{\beta}$ by treatment with Taxol was amplified by $p19^{ras}$ overexpression, which markedly increased caspase-3 dependent apoptosis in the p53-null SAOS2 cancer cell line. Our findings indicate a functional linkage between $p19^{ras}$ and p73 in caspase-3 mediated apoptosis of cancer cells.

• Bulletin of the Korean Chemical Society
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• 제33권1호
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• pp.227-232
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• 2012

Galectins are generally believed to be potential candidates for use in the development of novel antiinflammatory agents or as selective modulators of the immune response. In particular, galectin-9 exhibits some of the extracellular functions, including cell aggregation, adhesion, chemoattraction, activation, and apoptosis. Tl-galectin (Tl-gal, galectin-9 homologue gene) was isolated from an adult worm of the Toxascaris leonina. The full-length Tl-gal gene, which was incorporated into pET-28a, was overexpressed in E. coli and purified by nickel affinity and gel filtration chromatographies. The purified Tl-gal was crystallized using the hangingdrop vapor-diffusion method. The crystal belonged to the tetragonal space group $P4_1$, with unit-cell parameters of a = b = $75.7\AA$ and c = $248.4\AA$. The crystals were obtained at $20^{\circ}C$ and diffracted to a resolution of $3.0\AA$. The asymmetric unit contained four molecules of Tl-gal, which gave a crystal volume per protein mass (Vm) of $2.8\AA^3Da^{-1}$ and a solvent content of 54.1%.

• Molecules and Cells
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• 제37권6호
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• pp.480-486
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• 2014

Growth restriction by antibiotics is a common feature that pathogenic bacteria must overcome for survival. The struggle of bacteria to escape from growth restriction eventually results in development of antibiotic-resistance through the expression of a set of genes. Here we found that some physiologically important transcriptional regulators of Pseudomonas aeruginosa including QscR, a quorum sensing (QS) receptor, SoxR, a superoxide sensor-regulator, and AntR, a regulator of anthranilate-related secondary metabolism, are activated by various growth-restricted conditions. We generated the growth-restricted conditions by various methods, such as overexpression of PA2537 and treatment with antibiotics or disinfectants. The overexpression of PA2537, encoding an acyltransferase homologue, tightly restricted the growth of P. aeruginosa and significantly activated QscR during the growth restriction. Similarly, treatments with gentamycin, tetracycline, and ethanol also activated QscR near their minimal inhibitory concentrations (MICs). Some non-QS regulators, such as AntR and SoxR, were also activated near the MICs in the same conditions. However, LasR and PqsR, other QS receptors of P. aeruginosa, were not activated, suggesting that only a specific set of transcriptional regulators is activated by growth restriction. Since paraquat, a superoxide generator, significantly activated QscR and AntR, we suggest that the oxidative stress generated by growth restriction may be partly involved in this phenomenon.

• Journal of Microbiology and Biotechnology
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• 제30권11호
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• pp.1626-1639
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• 2020

In Caenorhabditis elegans, SHN-1 is the homologue of SHANK, a scaffolding protein. In this study, we determined the molecular basis for SHN-1/SHANK in the regulation of innate immune response to fungal infection. Mutation of shn-1 increased the susceptibility to Candida albicans infection and suppressed the innate immune response. After C. albicans infection for 6, 12, or 24 h, both transcriptional expression of shn-1 and SHN-1::GFP expression were increased, implying that the activated SHN-1 may mediate a protection mechanism for C. elegans against the adverse effects from fungal infection. SHN-1 acted in both the neurons and the intestine to regulate the innate immune response to fungal infection. In the neurons, GLR-1, an AMPA ionotropic glutamate receptor, was identified as the downstream target in the regulation of innate immune response to fungal infection. GLR-1 further positively affected the function of SER-7-mediated serotonin signaling and antagonized the function of DAT-1-mediated dopamine signaling in the regulation of innate immune response to fungal infection. Our study suggests the novel function of SHN-1/SHANK in the regulation of innate immune response to fungal infection. Moreover, our results also denote the crucial role of neurotransmitter signals in mediating the function of SHN-1/SHANK in regulating innate immune response to fungal infection.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 2003년도 정기총회 및 학술발표회
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• pp.50-50
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• 2003

We have identified and analysed a putative response regulator two-component gene (CaSKN7) from Candida albicans and its encoding protein (CaSkn7). CaSKN7 has an open reading frame of 1677bp. CaSKN7 encodes a 559 amino acid protein (CaSkn7) with an estimated molecular mass of 61.1 kDa. CaSKN7 is a homologue of a Saccharomyces cerevisiae SKN7 that is the regulator involved in the oxidative stress response. To study the role of CaSKN7, we constructed a CAI4-derived mutant strain carrying a homozygous deletion of the CaSKN7 gene. In the caskn7 disruptant cells, the formation of germ tube require shorter time than that in the congenic wild-type strain but the growth of mycelium delayed in liquid media. In contrast, the caskn7 disruptant cells attenuate the differentiation in solid media and the virulence in mouse model system. Expression level of hypha-specific and virulence genes - HYR1, ECE1, HWP1, and ALS1 - in the caskn7 disruptant cells increased as compared with that in the congenic wild-type strain in 10％ serum YPD. Skn7 in 5. cerevisiae was found to bind the HSE element from the SSA promoter, Also, CaSkn7 contains heat shock factor DNA-binding domain and the promoters of these genes have HSE-like sties. Therefore these results show that CaSKN7 regulate the differentiation and virulence of C. albicans.