• Journal of Gastric Cancer
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• 제5권1호
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• pp.34-39
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• 2005

목적: KLF6는 모든 조직에서 발현되고 있는 zinc finger를 가진 종양억제유전자로 인체 여러 암에서 불활성화되어 있다. 연구자들은 KLF6 단백의 발현 변화가 위암의 발생에 관여하는 지를 알아보고자 하였다. 대상 및 방법: 85예의 파라핀 포매된 위암조직에서 암세포들으 각각 3군데에서 펀치하여 새로운 파라핀 블록으로 옮겨 위암의 tissue microarray를 제작하였다. Tissue microarray 절편에서 KLF6 단백에 대한 항체로 면역화학염색을 실시한 후 발현 양상을 병리 지표들인 조직학적 소견, 침습 정도, 림프절 전이 및 복막파종 등과의 연관성을 조사하였다. 결과: KLF6 단백은 위점막의 표면과 소와 상피세포에서 주로 발현되고 있었고 85예 중 28예($28.9\%$)에서 발현 소실이 관찰되었다. 흥미롭게도 KLF6 단백의 발현 소실은 림프절 전이와 통계적으로 연관성이 있었으나 조직학적 소견, 침습 정도와 복막파종과는 연관성이 없었다. 결론: 이러한 소견들은 KLF6 단백의 발현 소실이 위장관 상피세포의 비정상적인 성장과 분화를 유도하고 위암의 발생 및 진행에 관여한다는 것을 의미한다.

• Journal of Gastric Cancer
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• 제19권4호
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• pp.460-472
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• 2019

Purpose: Long noncoding RNA 00703 (LINC00703) was found originating from a region downstream of Kruppel-like factor 6 (KLF6) gene, having 2 binding sites for miR-181a. Since KLF6 has been reported as a target of miR-181a in gastric cancer (GC), this study aims to investigate whether LINC00703 regulates the miR-181a/KLF6 axis and plays a functional role in GC pathogenesis. Materials and Methods: GC tissues, cell lines, and nude mice were included in this study. RNA binding protein immunoprecipitation (RIP) and pull-down assays were used to evaluate interaction between LINC00703 and miR-181a. Quantitative real-time polymerase chain reaction and western blot were applied for analysis of gene expression at the transcriptional and protein levels. A nude xenograft mouse model was used to determine LINC00703 function in vivo. Results: We revealed that LINC00703 competitively interacts with miR-181a to regulate KLF6. Overexpression of LINC00703 inhibited cell proliferation, migration/invasion, but promoted apoptosis in vitro, and arrested tumor growth in vivo. LINC00703 expression was found to be decreased in GC tissues, which was positively correlated with KLF6, but negatively with the miR-181a levels. Conclusions: LINC00703 may have an anti-cancer function via modulation of the miR-181a/KLF6 axis. This study also provides a new potential diagnostic marker and therapeutic target for GC treatment.

• 한국환경과학회지
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• 제29권4호
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• pp.423-434
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• 2020

The effects of amino acid and/or urea liquid fertilizer application on the growth and phytochemicals of Perilla leaves were summarized as follows; The fresh weight of the perilla leaves was in the order of CF, CL, KLF, and control, and 39.7 g, 37.4 g, 36.5 g and 32.3 g were measured. The plant height increased by 71.6 cm in the CF treatment than in the control(54.6 cm). The number of nodes was 14.3 node in CF treatment and 19% more than control(12 node). The vitamin C content tends to be increased by fertilizing the amino acid solution in the perilla leaf. The components of polyvalent unsaturation of n-6 origin were measured in CF treatment, KLF treatment, and control in 10.19 mg, 10.18 mg, and 9.38 mg per 100 g, respectively. Glutamic acid, aspartic acid, leucine, arginine, alanine and lysin were contained in perilla leaf amino acid. Glutaminic acid content was found to be 455.1 mg, 495.6 mg, and 478.8 mg in the control, KLF and CF treatment per 100 g, respectively. Effective nutrition management using amino acid fertilizer optimizes crop yield and profitability, it is important to reduce the negative environmental risks of using fertilizer.

• 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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• 제45권6호
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• pp.388-402
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• 2022

Malignant meningiomas often show invasive growth that makes complete tumor resection challenging, and they are more prone to recur after radical resection. Invasive meningioma associated transcript 1 (IMAT1) is a long noncoding RNA located on Homo sapiens chromosome 17 that was identified by our team based on absolute expression differences in invasive and non-invasive meningiomas. Our studies indicated that IMAT1 was highly expressed in invasive meningiomas compared with non-invasive meningiomas. In vitro studies showed that IMAT1 promoted meningioma cell invasion through the inactivation of the Krüppel-like factor 4 (KLF4)/hsa-miR22-3p/Snai1 pathway by acting as a sponge for hsa-miR22-3p, and IMAT1 knockdown effectively restored the tumor suppressive properties of KLF4 by preserving its tumor suppressor pathway. In vivo experiments confirmed that IMAT1 silencing could significantly inhibit the growth of subcutaneous tumors and prolong the survival period of tumor-bearing mice. Our findings demonstrated that the high expression of IMAT1 is the inherent reason for the loss of the tumor suppressive properties of KLF4 during meningioma progression. Therefore, we believe that IMAT1 may be a potential biological marker and treatment target for meningiomas.

• International Journal of Oral Biology
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• 제35권4호
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• pp.209-214
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• 2010

Cells that have endogenous multipotent properties can be used as a starting source for the generation of induced pluripotent cells (iPSC). In addition, small molecules associated with epigenetic reprogramming are also widely used to enhance the multi- or pluripotency of such cells. Skinderived precursor cells (SKPs) are multipotent, sphereforming and embryonic neural crest-related precursor cells. These cells can be isolated from a juvenile or adult mammalian dermis. SKPs are also an efficient starting cell source for reprogramming and the generation of iPSCs because of the high expression levels of Sox2 and Klf4 in these cells as well as their endogenous multipotency. In this study, valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, was tested in the generation of iPSCs as a potential enhancer of the reprogramming potential of SKPs. SKPs were isolated from the back skins of 5-6 week old C57BL/6 X DBA/2 F1 mice. After passage 3, the SKPs was treated with 2 mM of VPA and the quantitative real time RT-PCR was performed to quantify the expression of Oct4 and Klf4 (pluripotency specific genes), and Snai2 and Ngfr (neural crest specific genes). The results show that Oct4 and Klf4 expression was decreased by VPA treatment. However, there were no significant changes in neural crest specific gene expression following VPA treatment. Hence, although VPA is one of the most potent of the HDAC inhibitors, it does not enhance the reprogramming of multipotent skin precursor cells in mice.

• Journal of Microbiology and Biotechnology
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• 제24권6호
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• pp.869-878
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• 2014

In this study, we performed two-dimensional electrophoresis with protein extracts from lizard tails, and analyzed the protein expression profiles during the tissue regeneration to identify the dedifferentiation factor. As a result, we identified 18 protein spots among total of 292 spots, of which proteins were specifically expressed during blastema formation. We selected lactoferrin as a candidate because it is the mammalian homolog of leech-derived tryptase inhibitor, which showed the highest frequency among the 18 proteins. Lactoferrin was specifically expressed in various stem cell lines, and enhanced the efficiency of iPSC generation upto approximately 7-fold relative to the control. Furthermore, lactoferrin increased the efficiency by 2-fold without enforced expression of Klf4. These results suggest that lactoferrin may induce dedifferentiation, at least partly by increasing the expression of Klf4.

• 전기학회논문지
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• 제57권6호
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• pp.1026-1031
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• 2008

We report on the design and experimental results of a large diameter faraday rotator for the high-power laser system(KLF: Kaeri laser facility) that was completed in late 2007s at Korea Atomic Energy Research Institute. The design involves modelling the magnetic field of cylindrical coil with large diameter(110 mm). Magnetic field generation coil is designed by 6 layers using a rectangular wire with cross-sectional area $3{\times}5[mm^2]$. We obtain an isolation ratio for optical feedback of 35 dB at 1064 nm and magnetic field strengths ${\sim}25kG$. We expect that the design can be widely used optical isolators in high-power laser system.

• 한국식품과학회지
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• 제50권6호
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• pp.688-696
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• 2018

본 연구에서는 홍삼 사포닌 분획(SF)으로부터 진세노사이드의 조성을 분석하고 지방세포의 분화 및 지방축적에 대한 효과를 측정하였다. SF는 지방분화인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$의 단백질 양을 억제함으로써 지방분화 동안 효과적으로 지방축적을 억제하였으며 주로 지방분화 초기시점부터 지방분화 초기인자인 $C/EBP{\beta}$, KLF2의 조절작용을 통해 지방축적을 억제하는 것으로 관찰되었다. SF는 또한 지방분화 동안 생성되는 ROS의 생성을 효과적으로 억제하였는데 이는 SF가 산화방지 시스템인 Nrf2/Keap1 경로를 활성화하기 때문으로 판단되며 특히 Nrf2의 핵 내로의 진입을 활성화 함으로써 Nrf2의 타겟 산화방지 분자들인 HO-1, NQO1의 발현을 촉진하였다. 이는 지방분화 동안 SF의 지방축적 억제 효과가 Nrf2의 활성화와 밀접하게 관련이 있음을 보여준다.

• 대한임상검사과학회지
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• 제47권4호
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• pp.298-305
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• 2015

최근 종양을 극복하고자 하는 새로운 접근 방법가운데 하나로, 종양세포내에 발현되는 줄기세포 전사인자들(Oct4, Sox2, KLF4 and Lin28)을 억제하여 종양을 치료하는 연구들이 증가하고 있다. 본 실험은 미분화 전사인자를 표적(조절)하는 microRNA-126을 이용하여 난소종양세포들(6종: HSC832(t)c, Ovcar3, Skov3, PA-1, TOV21G and Tov112D)들 생존과 성장에 어떠한 생물학적 변화를 유도하는지 연구하였다. Scramble과 microRNA-126를 난소종양세포들에 처리 후 세포모양 관찰결과 Skov3를 제외한 난소 종양세포들에서 형태학적 모양 변성과 부유현상을 관찰하였다. CCK-8을 이용한 세포분열능 분석에서 Skov3를 제외한 난소 종양세포들의 분열능력이 점차적으로 감소되는 것을 확인하였다. 특히 Tov112D, Tov21G and PA-1에서 각 시간대별로 뚜렷한 세포분열 능력 감소를 확인할 수 있었다. RT-PCR결과 미분화 전사인자들(Sox2, Lin28)의 발현감소를 확인할 수 있었다. 이러한 결과들은 microRNA-126이 다양한 난소 종양세포들을 표적하여 세포분열능과 사멸을 유도할 수 있는 가역적 환경(유전자 발현조절)을 제공함과 동시에 임상 치료에 대한 분자생물학적 단서를 제공할 수 있을 것이다.