• Asian Pacific Journal of Cancer Prevention
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• 제14권9호
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• pp.5055-5060
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• 2013

Objective: Twist, a basic helix-loop-helix transcription factor, plays a key role in the metastatic progression of human cancer. Matrix metalloproteinase (MMP)-9 is an endopeptidase that digests basement membrane type IV collagen, therefore being possibly related to tumor progression. It has been reported that Twist and matrix metalloproteinase-9 (MMP-9) are expressed in gastric cancers. However, the exact roles of Twist and MMP-9 in tumor metastasis and prognosis remain unclear. The aim of this study was to casts light on this question. Methods:Twist and MMP-9 expression in tissue sections of 37 gastric carcinomas was evaluated with immunohistochemistry. The staining results were compared with clinicopatholgic features and to patients' outcome. Results: Twist positive expression was significantly increased in gastric cancer cases with lymph node metastasis (P=0.023). But no correlations were found between MMP-9 overexpression and clinicopathologic features, such as recurrence, TNM stage, and lymph node metastasis. Overall survival (OS) was significantly correlated with recurrence, serosa invasion, TNM stages, distant metastasis, and MMP-9 (P=0.027, 0.021, 0.000, 0.024 and 0.036, respectively). Disease-free survival (DFS) was prominently related to recurrence location, serosa invasion and TNM stages (P=0.000, 0.038 and 0.003, respectively). In the Cox regression multivariate analysis, TNM stage, distant metastasis and MMP-9 were significantly associated with prognosis of gastric cancer (P=0.002, 0.019, and 0.032, respectively). Conclusions: This study showed Twist positive expression to be significantly correlated with lymph node metastasis in gastric cancer. MMP-9 overexpression is associated with OS, suggesting that MMP-9 is a prognostic indicator for survival in patients with gastric cancer.

• BMB Reports
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• 제41권10호
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• pp.693-698
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• 2008

The full-length cDNA of LebZIP2 (Lycopersicon esculentum bZIP2) encodes a protein of 164 amino acids and contains a N-terminal basic-region leucine zipper domain. Analysis of the deduced tomato LebZIP2 amino acid sequence revealed that it shares 85% sequence identity with both tobacco bZIP and pepper CcbZIP. LebZIP2 mRNA is expressed at a high level exclusively in flowers. Presently, LebZIP2 was strongly increased also following NaCl and mannitol treatments. No significant LebZIP2 expression was evident following cold treatment. Transient LebZIP2 overexpression resulted in increased NbNOA1 and NbNR transcript levels in Nicotiana benthamiana leaves. Our results indicate that LebZIP2 might play roles as an abiotic stress-signaling pathway and as a transcriptional regulator of the NbNOA1 or NbNR genes.

• Molecules and Cells
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• 제21권3호
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• pp.367-375
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• 2006

We previously identified a novel cancer/testis antigen gene CAGE by screening cDNA expression libraries of human testis and gastric cancer cell lines with sera of gastric cancer patients. CAGE is expressed in many cancers and cancer cell lines, but not in normal tissues apart from the testis. In the present study, we investigated its role in the motility of cells of two human cancer cell lines: HeLa and the human hepatic cancer cell line, SNU387. Induction of CAGE by tetracycline or transient transfection enhanced the migration and invasiveness of HeLa cells, but not the adhesiveness of either cell line. Overexpression of CAGE led to activation of ERK and p38 MAPK but not Akt, and inhibition of ERK by PD98059 or p38 MAPK by SB203580 counteracted the CAGE-promoted increase in motility in both cell lines. Overexpression of CAGE also resulted in a reduction of ROS and an increase of ROS scavenging, associated with induction of catalase activity. Inhibition of ERK and p38 MAPK increased ROS levels in cells transfected with CAGE, suggesting that ROS reduce the motility of both cell lines. Inhibition of ERK and p38 MAPK reduced the induction of catalase activity resulting from overexpression of CAGE, and inhibition of catalase reduced CAGE-promoted motility. We conclude that CAGE enhances the motility of cancer cells by activating ERK and p38 MAPK, inducing catalase activity, and reducing ROS levels.

• Molecules and Cells
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• 제21권3호
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• pp.418-427
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• 2006

Ionotropic glutamate receptors (iGluRs) are ligand-gated nonselective cation channels that mediate fast excitatory neurotransmission. Although homologues of the iGluRs have been identified in higher plants, their roles are largely unknown. In this work we isolated a full-length cDNA clone (RsGluR) encoding a putative glutamate receptor from small radish. An RsGluR:mGFP fusion protein was localized to the plasma membrane. In Arabidopsis thaliana overexpressing the fulllength cDNA, glutamate treatment triggered greater $Ca^{2+}$ influx in the root cells of transgenic seedlings than in those of the wild type. Transgenic plants exhibited multiple morphological changes such as necrosis at their tips and the margins of developing leaves, dwarf stature with multiple secondary inflorescences, and retarded growth, as previously observed in transgenic Arabidopsis overexpressing AtGluR3.2 [Kim et al. (2001)]. Microarray analysis showed that jasmonic acid (JA)-responsive genes including defensins and JA-biosynthetic genes were up-regulated. RsGluR overexpression also inhibited growth of a necrotic fungal pathogen Botrytis cinerea possibly due to up-regulation of the defensins. Based on these results, we suggest that RsGluR is a glutamate-gated $Ca^{2+}$ channel located in the plasma membrane of higher plants and plays a direct or indirect role in defense against pathogen infection by triggering JA biosynthesis.

• International Journal of Oral Biology
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• 제43권3호
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• pp.161-169
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• 2018

We previously demonstrated that epidermal growth factor (EGF) enhances cell migration and invasion of breast cancer cells in a SMAD ubiquitination regulatory factor 1 (SMURF1)-dependent manner and that SMURF1 induces degradation of ${\beta}-catenin$ in C2C12 cells. However, the relationship between EGF-induced SMURF1 and ${\beta}-catenin$ expression in breast cancer cells remains unclear. So, we investigated if EGF and SMURF1 regulate ${\beta}-catenin$ expression in MDAMB231 human breast cancer cells. When MDAMB231 cells were incubated with EGF for 24, 48, and 72 hours, EGF significantly increased expression levels of SMURF1 mRNA and protein while suppressing expression levels of ${\beta}-catenin$ mRNA and protein. Overexpression of SMURF1 downregulated ${\beta}-catenin$ mRNA and protein, whereas knockdown of SMURF1 increased ${\beta}-catenin$ expression and blocked EGF-induced ${\beta}-catenin$ downregulation. Knockdown of ${\beta}-catenin$ enhanced cell migration and invasion of MDAMB231 cells, while ${\beta}-catenin$ overexpression suppressed EGF-induced cell migration and invasion. Furthermore, knockdown of ${\beta}-catenin$ enhanced vimentin expression and decreased cytokeratin expression, whereas ${\beta}-catenin$ overexpression decreased vimentin expression and increased cytokeratin expression. These results suggest that EGF downregulates ${\beta}-catenin$ in a SMURF1-dependent manner and that ${\beta}-catenin$ downregulation contributes to EGF-induced cell migration and invasion in MDAMB breast cancer cells.

• Journal of Ginseng Research
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• 제44권2호
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• pp.321-331
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• 2020

Background: The patatin-related phospholipase AIII family (pPLAIIIs) genes alter cell elongation and cell wall composition in Arabidopsis and rice plant, suggesting diverse commercial purposes of the economically important medicinal ginseng plant. Herein, we show the functional characterization of a ginseng pPLAIII gene for the first time and discuss its potential applications. Methods: pPLAIIIs were identified from ginseng expressed sequence tag clones and further confirmed by search against ginseng database and polymerase chain reaction. A clone showing the highest homology with pPLAIIIβ was shown to be overexpressed in Arabidopsis using Agrobacterium. Quantitative polymerase chain reaction was performed to analyze ginseng pPLAIIIβ expression. Phenotypes were observed using a low-vacuum scanning electron microscope. Lignin was stained using phloroglucinol and quantified using acetyl bromide. Results: The PgpPLAIIIβ transcripts were observed in all organs of 2-year-old ginseng. Overexpression of ginseng pPLAIIIβ (PgpPLAIIIβ-OE) in Arabidopsis resulted in small and stunted plants. It shortened the trichomes and decreased trichome number, indicating defects in cell polarity. Furthermore, OE lines exhibited enlarged seeds with less number per silique. The YUCCA9 gene was downregulated in the OE lines, which is reported to be associated with lignification. Accordingly, lignin was stained less in the OE lines, and the expression of two transcription factors related to lignin biosynthesis was also decreased significantly. Conclusion: Overexpression of pPLAIIIβ retarded cell elongation in all the tested organs except seeds, which were longer and thicker than those of the controls. Shorter root length is related to auxinresponsive genes, and its stunted phenotype showed decreased lignin content.

• Molecules and Cells
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• 제41권6호
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• pp.575-581
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• 2018

Postmenopausal osteoporosis (PMOP) is a common systemic skeletal disease characterized by reduced bone mass and microarchitecture deterioration. Although differentially expressed SOX5 has been found in bone marrow from ovariectomized mice, its role in osteogenic differentiation in human mesenchymal stem cells (hMSCs) from bone marrow in PMOP remains unknown. In this study, we investigated the biological function of SOX5 and explore its molecular mechanism in hMSCs from patients with PMOP. Our findings showed that the mRNA and protein expression levels of SOX5 were upregulated in hMSCs isolated from bone marrow samples of PMOP patients. We also found that SOX5 overexpression decreased the alkaline phosphatase (ALP) activity and the gene expression of osteoblast markers including Collagen I, Runx2 and Osterix, which were increased by SOX5 knockdown using RNA interference. Furthermore, $TNF-{\alpha}$ notably upregulated the SOX5 mRNA expression level, and SOX5 knockdown reversed the effect of $TNF-{\alpha}$ on osteogenic differentiation of hMSCs. In addition, SOX5 overexpression increased Kruppel-like factor 4 (KLF4) gene expression, which was decreased by SOX5 silencing. KLF4 knockdown abrogated the suppressive effect of SOX5 overexpression on osteogenic differentiation of hMSCs. Taken together, our results indicated that $TNF-{\alpha}$-induced SOX5 upregulation inhibited osteogenic differentiation of hMSCs through KLF4 signal pathway, suggesting that SOX5 might be a novel therapeutic target for PMOP treatment.

• Molecules and Cells
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• 제42권10호
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• pp.693-701
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• 2019

Plants monitor changes in day length to coordinate their flowering time with appropriate seasons. In Arabidopsis, the diel and seasonal regulation of CONSTANS (CO) protein stability is crucial for the induction of FLOWERING LOCUS T (FT) gene in long days. FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1) and ZEITLUPE (ZTL) proteins control the shape of CO expression profile antagonistically, although regulation mechanisms remain unknown. In this study, we show that GIGANTEA (GI) protein modulates the stability and nuclear function of FKF1, which is closely related to the stabilization of CO in the afternoon of long days. The abundance of FKF1 protein is decreased by the gi mutation, but increased by GI overexpression throughout the day. Unlike the previous report, the translocation of FKF1 to the nucleus was not prevented by ZTL overexpression. In addition, the FKF1-ZTL complex formation is higher in the nucleus than in the cytosol. GI interacts with ZTL in the nucleus, implicating the attenuation of ZTL activity by the GI binding and, in turn, the sequestration of FKF1 from ZTL in the nucleus. We also found that the CO-ZTL complex presents in the nucleus, and CO protein abundance is largely reduced in the afternoon by ZTL overexpression, indicating that ZTL promotes CO degradation by capturing FKF1 in the nucleus under these conditions. Collectively, our findings suggest that GI plays a pivotal role in CO stability for the precise control of flowering by coordinating balanced functional properties of FKF1 and ZTL.

• BMB Reports
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• 제52권9호
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• pp.566-571
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• 2019

Lymphoma is one of the most curable types of cancer. However, drug resistance is the main challenge faced in lymphoma treatment. Peroxisomal acyl-CoA oxidase 1 (ACOX1) is the rate-limiting enzyme in fatty acid ${\beta}$-oxidation. Deregulation of ACOX1 has been linked to peroxisomal disorders and carcinogenesis in the liver. Currently, there is no information about the function of ACOX1 in lymphoma. In this study, we found that upregulation of ACOX1 promoted proliferation in lymphoma cells, while downregulation of ACOX1 inhibited proliferation and induced apoptosis. Additionally, overexpression of ACOX1 increased resistance to doxorubicin, while suppression of ACOX1 expression markedly potentiated doxorubicin-induced apoptosis. Interestingly, downregulation of ACOX1 promoted mitochondrial location of Bad, reduced mitochondrial membrane potential and provoked apoptosis by activating caspase-9 and caspase-3 related apoptotic pathway. Overexpression of ACOX1 alleviated doxorubicin-induced activation of caspase-9 and caspase-3 and decrease of mitochondrial membrane potential. Importantly, downregulation of ACOX1 increased p73, but not p53, expression. p73 expression was critical for apoptosis induction induced by ACOX1 downregulation. Also, overexpression of ACOX1 significantly reduced stability of p73 protein thereby reducing p73 expression. Thus, our study indicated that suppression of ACOX1 could be a novel and effective approach for treatment of lymphoma.

• Molecules and Cells
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• 제42권5호
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• pp.406-417
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• 2019

RICE FLOWERING LOCUS T 1 (RFT1) is a major florigen that functions to induce reproductive development in the shoot apical meristem (SAM). To further our study of RFT1, we overexpressed the gene and examined the expression patterns of major regulatory genes during floral transition and inflorescence development. Overexpression induced extremely early flowering in the transgenics, and a majority of those calli directly formed spikelets with a few spikelets, thus bypassing normal vegetative development. FRUITFULL (FUL)-clade genes OsMADS14, OsMADS15, and OsMADS18 were highly induced in the RFT1-expressing meristems. OsMADS34 was also induced in the meristems. This indicated that RFT1 promotes the expression of major regulatory genes that are important for inflorescence development. RFT1 overexpression also induced SEPALLATA (SEP)-clade genes OsMADS1, OsMADS5, and OsMADS7 in the greening calli before floral transition occurred. This suggested their possible roles at the early reproductive stages. We found it interesting that expression of OsFD1 as well as OsFD2 and OsFD3 was strongly increased in the RFT1-expressing calli and spikelets. At a low frequency, those calli produced plants with a few leaves that generated a panicle with a small number of spikelets. In the transgenic leaves, the FUL-clade genes and OsMADS34 were induced, but SEP-clade gene expression was not increased. This indicated that OsMADS14, OsMADS15, OsMADS18, and OsMADS34 act immediately downstream of RFT1.