• BMB Reports
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• 제50권4호
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• pp.220-225
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• 2017

Antisense transcripts were initially identified as transcriptional noise, but have since been reported to play an important role in the quality control of miRNA functions. In this report, we tested the hypothesis that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulates miRNA function via competitive endogenous RNAs, such as pseudogenes, long non-coding RNAs, and antisense transcripts. Based on analyses of RNA sequencing data, the knockdown of hnRNPK decreased the antisense PTOV1-AS1 transcript which harbors five binding sites for miR-1207-5p. We identified heme oxygenase-1 (HO-1) mRNA as a novel target of miR-1207-5p by western blotting and Ago2 immunoprecipitation. The knockdown of hnRNPK or PTOV1-AS1 suppressed HO-1 expression by increasing the enrichment of HO-1 mRNA in miR-1207-5p-mediated miRISC. Downregulation of HO-1 by a miR-1207-5p mimic or knockdown of hnRNPK and PTOV1-AS1 inhibited the proliferation and clonogenic ability of HeLa cells. Taken together, our results demonstrate that hnRNPK-regulated PTOV1-AS1 modulates HO-1 expression via miR-1207-5p.

• BMB Reports
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• 제53권4호
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• pp.173-180
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• 2020

Galectin-3 is a carbohydrate-binding protein and regulates diverse functions, including cell proliferation and differentiation, mRNA splicing, apoptosis induction, immune surveillance and inflammation, cell adhesion, angiogenesis, and cancer-cell metastasis. Galectin-3 is also recommended as a diagnostic or prognostic biomarker of various diseases, including heart disease, kidney disease, and cancer. Galectin-3 exists as a cytosol, is secreted in extracellular spaces on cells, and is also detected in nuclei. It has been found that galectin-3 has different functions in cellular localization: (i) Extracellular galectin-3 mediates cell attachment and detachment. (ii) cytosolic galectin-3 regulates cell survival by blocking the intrinsic apoptotic pathway, and (iii) nuclear galectin-3 supports the ability of the transcriptional factor for target gene expression. In this review, we focused on the role of galectin-3 on translocation from cytosol to nucleus, because it happens in a way independent of carbohydrate recognition and accelerates cancer progression. We also suggested here that intracellular galecin-3 could be a potent therapeutic target in cancer therapy.

• Fisheries and Aquatic Sciences
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• 제24권1호
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• pp.1-9
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• 2021

Human prostate cancer is the second most frequently diagnosed cancer worldwide, and its incidence rate continues to increase. Advanced prostate cancer is more difficult to treat than early forms due to its chemotherapy resistance. There is need for more effective agents that can inhibit the progression of advanced prostate cancer. Demethoxyfumitremorgin C (DMFTC) was isolated from the fermentation extract of the marine fungus Aspergillus fumigatus. Antiproliferative activity of DMFTC against human prostate cancer PC3 cells was examined through cell cycle analysis by flow cytometry, the fluorescent nuclear imaging analysis with propidium iodide (PI), and proteins expression related to cell cycle arrest and apoptosis were investigated via Western blotting. DMFTC inhibited PC3 cells growth through G1 phase cell cycle arrest and apoptosis induction. It activated the tumor suppressor p53 and the Cdk inhibitor p21, which regulate the cell progression into the G1 phase. Additionally, PI-positive late apoptotic non-viable cells were increased and the expression levels of the G1-positive downstream regulators cyclin D, cyclin E, Cdk2, and Cdk4 were decreased by DMFTC treatment. These results suggest that DMFTC induces G1 arrest and apoptosis induction through regulation of p53/p21-dependent cyclin-Cdk complexes, and it may be a useful therapeutic agent for the treatment of human advanced prostate cancer.

• 방사성폐기물학회지
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• 제19권4호
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• pp.447-457
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• 2021

Graphite Isotope Ratio Method (GIRM) can be used to estimate plutonium production in a graphite-moderated reactor. This study presents verification results for the GIRM combined with a 3-D polynomial regression function to estimate cumulative plutonium production in a graphite-moderated reactor. Using the 3-D Monte-Carlo method, verification was done by comparing the cumulative plutonium production with the GIRM. The GIRM can estimate plutonium production for specific sampling points using a function that is based on an isotope ratio of impurity elements. In this study, the ¹⁰B/¹¹B isotope ratio was chosen and calculated for sampling points. Then, 3-D polynomial regression was used to derive a function that represents a whole core cumulative plutonium production map. To verify the accuracy of the GIRM with polynomial regression, the reference value of plutonium production was calculated using a Monte-Carlo code, MCS, up to 4250 days of depletion. Moreover, the amount of plutonium produced in certain axial layers and fuel pins at 1250, 2250, and 3250 days of depletion was obtained and used for additional verification. As a result, the difference in the total cumulative plutonium production based on the MCS and GIRM results was found below 3.1% with regard to the root mean square (RMS) error.

• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2425-2430
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• 2015

Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. EHZ2 is involved in drug resistance and is overexpressed in drug-resistant cancer cell lines. In this study, we investigated the effects of EHZ2 on cisplatin -resistance in A549/DDP and AGS/DDP cells. EHZ2 mRNA and protein were found to be significantly overexpressed in A549/DDP and AGS/DDP cells, compared to parental cells. EHZ2 siRNA successfully silenced EHZ2 mRNA and protein expression. Proliferation was inhibited and drug resistance to cisplatin was improved. Flow cytometry showed that silencing of EHZ2 arrested A549/DDP and AGS/DDP cells in the G0/G1 phase, increasing apoptosis, rh-123 fluorescence intensity and caspase-3/8 activities. Silencing of EHZ2 also significantly reduced the mRNA and protein expression levels of cyclin D1 and MDR1,while up-regulating p15, p21, p27 and miR-218 in A549/DPP cells. Furthermore, silencing of EHZ2 also significantly increased the expression level of tumor suppressor factor miR-218. We also found down-regulating EHZ2 expression increased methylation in A549/DDP and AGS/DDP cells. This study demonstrates that drug resistance can be effectively reversed in human cisplatin-resistant lung and gastric cancer cells through delivery of siRNAs targeting EHZ2.

• 방사성폐기물학회지
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• 제18권1호
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• pp.83-90
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• 2020

흑연 동위원소 비율법(GIRM)은 비핵화 검증 도구로써 흑연감속로의 플루토늄 생산량을 예측하는데 사용된다. 원자로가 가동되면 ²³⁸U의 중성자 포획 반응에 의해 플루토늄이 생성되어 축적되고 동시에 흑연 내 불순물도 핵반응을 통해 다른 핵종으로 바뀌기 때문에 플루토늄의 생성량과 불순물의 농도는 일정한 상관 관계를 갖는다. 이러한 상관관계에도 불구하고 어느 특정 시점에서의 불순물의 농도는 불순물의 초기 농도에 의존하기 때문에 불순물의 초기 농도가 알려지지 않으면 불순물의 절대 농도만으로 플루토늄 생산량을 예측하는 것은 불가능하다. 그러나 불순물의 초기 동위원소 비율은 초기 불순물 농도에 상관없이 알려져 있기 때문에 불순물의 동위원소 비율과 플루토늄 생산량의 관계는 흑연감속로에서 플루토늄 생성량을 예측하는 유용한 도구가 될 수 있다. 흑연동위원소 비율법의 지표 원소로 Boron, Lithium, Chlorine, Titanium, Uranium 등이 이용되는 것으로 알려져 있다. 위 지표원소의 동위원소 비와 플루토늄 생성량 사이의 상관 관계가 초기 불순물 농도에 의존하지 않는지를 네 가지 다른 흑연 불순물 조성을 이용하여 평가하였다. ¹⁰B/¹¹B, ³⁶Cl/³⁵Cl, ⁴⁸Ti/⁴⁹Ti, ²³⁵U/²³⁸U은 흑연의 초기 불순물 농도에 상관없이 누적 플루토늄 생성량과 일관된 상관 관계를 갖는다. 이러한 원소들은 다른 원소의 핵반응에 의해 해당 원소의 동위원소가 생성되지 않기 때문이다. 반면 ⁶Li/⁷Li과 플루토늄 생성량의 상관관계는 흑연 내 불순물의 초기 농도에 의존한다. ⁷Li은 ⁶Li의 중성자 포획 반응에 의해서 생성되기도 하지만 ¹⁰B의 (n, α)반응으로도 생성되는 것이 더 지배적이기 때문에 ¹⁰B의 초기 농도가 ⁷Li의 생성량에 영향을 미치는 것이다. 따라서 Lithium은 흑연 동위원소 비율법을 위한 지표 원소로 적절하지 않음을 알 수 있다.

• 한국수정란이식학회지
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• 제31권1호
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• pp.1-7
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• 2016

Xenotransplantation involves multiple steps of immune rejection. The present study was designed to produce nuclear transfer embryos, prior to the production of transgenic pigs, using fibroblasts carrying transgenes human complement regulatory protein hCD59 and interleukin-18 binding protein (hIL-18BP) to reduce hyperacute rejection (HAR) and cellular rejection in pig-to-human xenotransplantation. In addition to the hCD59-mediated reduction of HAR, hIL-18BP may prevent cellular rejection by inhibiting the activation of natural killer cells, activated T-cell proliferation, and induction of $IFN-{\gamma}$. Transgene construct including hCD59 and ILI-18BP was introduced into miniature pig fetal fibroblasts. After antibiotic selection of double transgenic fibroblasts, integration of the transgene was screened by PCR, and the transgene expression was confirmed by RT-PCR. Treatment of human serum did not affect the survival of double-transgenic fibroblasts, whereas the treatment significantly reduced the survival of non-transgenic fibroblasts (p<0.01), suggesting alleviation of HAR. Among 337 reconstituted oocytes produced by nuclear transfer using the double transgenic fibroblasts, 28 (15.3%) developed to the blastocyst stage. Analysis of individual embryos indicated that 53.6% (15/28) of embryos contained the transgene. The result of the present study demonstrates the resistance of hCD59 and IL-18BP double-transgenic fibroblasts against HAR, and the usefulness of the transgenic approach may be predicted by RT-PCR and cytolytic assessment prior to actual production of transgenic pigs. Further study on the transfer of these embryos to surrogates may produce transgenic clone miniature pigs expressing hCD59 and hIL-18BP for xenotransplantation.

• Journal of Radiation Protection and Research
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• 제39권1호
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• pp.54-60
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• 2014

IAEA는 핵물질 계량 관리 검사를 위해 다양한 방사선 검출기를 사용하고 있다. 주로 HPGe, NaI(Tl), CZT 등이 사용되며, 정확한 측정이 요구되는 검사에는 고분해능 HPGe 검출기 활용도가 높다. HPGe 검출기는 추가적인 냉각장치로 인하여 부피가 크고 무거우며, 사용하기 전에 충분히 냉각시켜야 하기 때문에 측정의 준비 시간이 많이 걸린다는 단점이 있다. 이러한 문제점을 해결하기 위해 가볍고 짧은 사용 전 냉각이 요구되는 휴대형 HPGe가 개발되었다. 본 논문은 개발된 휴대형 HPGe 검출기 시제품을 실제 IAEA 사찰 현장에 적용하여 얻은 성능평가 결과를 기술한다. 휴대형 HPGe로 얻은 방사선 스펙트럼은 핵물질 종류와 농축도에 따라 다른 특징을 보였고, 또한 $^{235}U$과 $^{238}U$의 붕괴 계열에서 방출되는 감마선 및 우라늄의 특성 x-선 차이도 확인할 수 있었다. 그리고 휴대형 HPGe 검출기 시제품으로 측정한 농축도는 핵물질 종류에 따라 실제값과 9 ~ 27%의 상대적 오차를 보였다. 휴대형이라는 소형 검출기의 한계 때문에 일부 핵물질은 IAEA에서 요구하는 정확도를 만족시키지 못하는 경우도 있었지만 향후 추가적인 연구의 수행으로 이러한 문제점은 해결 가능할 것으로 판단된다. 본 논문은 새로운 휴대형 HPGe 검출기를 안전조치에 적용한 사례와 측정한 스펙트럼을 농축도 분석 코드로 분석한 결과를 다룬다. 따라서 국내 원자력시설의 우라늄 농축도 검증을 위한 IAEA 안전조치 사찰 결과를 분석한 논문이 별로 발표되지 않은 상황에서, 본 논문은 안전조치 검사 결과 분석에도 유익할 것으로 판단된다. 개발된 방사선 검출기의 개선 사항도 함께 논의하였으므로 향후 관련 분야 방사선 검출기 개발에도 기여할 것으로 예상된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1219-1225
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• 2014

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol molecule from green tea and is known to exhibit antioxidative as well as tumor suppressing activity. In order to examine EGCG tumor invasion and suppressing activity against adult T-cell leukemia (ATL), two HTLV-1 positive leukemia cells (HuT-102 and C91-PL) were treated with non-cytotoxic concentrations of EGCG for 2 and 4 days. Proliferation was significantly inhibited by 100 ${\mu}M$ at 4 days, with low cell lysis or cytotoxicity. HTLV-1 oncoprotein (Tax) expression in HuT-102 and C91-PL cells was inhibited by 25 ${\mu}M$ and 125 ${\mu}M$ respectively. The same concentrations of EGCG inhibited NF-kB nuclearization and stimulation of matrix metalloproteinase-9 (MMP-9) expression in both cell lines. These results indicate that EGCG can inhibit proliferation and reduce the invasive potential of HTLV-1-positive leukemia cells. It apparently exerted its effects by suppressing Tax expression, manifested by inhibiting the activation of NF-kB pathway and induction of MMP-9 transcription in HTLV-1 positive cells.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3519-3528
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• 2012

Inhibitory effects of Maclura amboinenesis Bl, one plant used traditionally for the treatment of cancers, on metastatic potential of highly metastatic B16F10 melanoma cells were investigated in vitro. Cell proliferation was assessed using the MTT colorimetric assay. Details of metastatic capabilities including invasion, migration and adhesion of B16F10 melanoma cells were examined by Boyden Chamber invasion and migration, scratch motility and cell attachment assays, respectively. The results demonstrated that n-hexane and chloroform extracts exhibited potent anti-proliferative effects (p<0.01), whereas the methanol and aqueous extracts had less pronounced effects after 24 h exposure. Bioactivity-guided chromatographic fractionation of both active n-hexane and chloroform extracts led to the isolation of two main prenylated xanthones and characterization as macluraxanthone and gerontoxanthone-I, respectively, their structures being identified by comparison with the spectral data. Interestingly, both exhibited potent effective effects. At non-toxic effective doses, n-hexane and chloroform extracts (10 and $30{\mu}g/ml$) as well as macluraxanthone and gerontoxanthone-I (3 and $10{\mu}M$) significantly inhibited B16F10 cell invasion, to a greater extent than $10{\mu}m$ doxorubicin, while reducing migration of cancer cells without cellular cytotoxicity. Moreover, exposure of B16F10 melanoma cells to high concentrations of chloroform ($30{\mu}g/ml$) and geratoxanthone-I ($20{\mu}M$) for 24 h resulted in delayed adhesion and retarded colonization. As insights into mechanisms of action, typical morphological changes of apoptotic cells e.g. membrane blebbing, chromatin condensation, nuclear fragmentation, apoptotic bodies and loss of adhesion as well as cell cycle arrest in the G1 phase with increase of sub-G1 cell proportions, detected by Hoechst 33342 staining and flow cytometry were observed, suggesting DNA damage and subsequent apoptotic cell death. Taken together, our findings indicate for the first time that active n-hexane and chloroform extracts as well as macluraxanthone and gerontoxanthone-I isolated from Maclura amboinensis Bl. roots affect multistep of cancer metastasis processes including proliferation, adhesion, invasion and migration, possibly through induction of apoptosis of highly metastatic B16F10 melanoma cells. Based on these data, M. amboinensis Bl. represents a potential candidate novel chemopreventive and/or chemotherapeutic agent. Additionally, they also support its ethno-medicinal usage for cancer prevention and/or chemotherapy.