Phenylpropanoids in radioregulation: double edged sword

김완연,윤부현,Ki Moon Seong 생화학분자생물학회 2011 Experimental and molecular medicine Vol.43 No.6

Radiotherapy, frequently used for treatment of solid tumors,carries two main obstacles including acquired radioresistance in cancer cells during radiotherapy and normal tissue injury. Phenylpropanoids, which are naturally occurring phytochemicals found in plants,have been identified as potential radiotherapeutic agents due to their anti-cancer activity and relatively safe levels of cytotoxicity. Various studies have proposed that these compounds could not only sensitize cancer cells to radiation resulting in inhibition of growth and cell death but also protect normal cells against radiation-induced damage. This review is intended to provide an overview of recent investigations on the usage of phenylpropanoids in combination with radiotherapy in cancer treatment.

RNF138-mediated ubiquitination of rpS3 is required for resistance of glioblastoma cells to radiation-induced apoptosis

김완연,윤혜숙,이성민,김은기,김대훈,이정섭,이제명,윤부현 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or macrophage migration inhibitory factor in non-small-cell lung cancer is responsible for radioresistance. However, the role of rpS3 in glioblastoma (GBM) has not been investigated to date. Here we found that in irradiated GBM cells, rpS3 translocated into the nucleus and was subsequently ubiquitinated by ring finger protein 138 (RNF138). Ubiquitin-dependent degradation of rpS3 consequently led to radioresistance in GBM cells. To elucidate the apoptotic role of rpS3, we analyzed the interactome of rpS3 in ΔRNF138 GBM cells. Nuclear rpS3 interacted with DNA damage inducible transcript 3 (DDIT3), leading to DDIT3-induced apoptosis in irradiated ΔRNF138 GBM cells. These results were confirmed using in vivo orthotopic xenograft models and GBM patient tissues. This study aims to clarify the role of RNF138 in GBM cells and demonstrate that rpS3 may be a promising substrate of RNF138 for the induction of GBM radioresistance, indicating RNF138 as a potential target for GBM therapy.

TFAP2C-mediated upregulation of TGFBR1 promotes lung tumorigenesis and epithelial–mesenchymal transition

김완연,김은기,이성민,김대훈,천자현,박강현,윤혜숙,윤부현 생화학분자생물학회 2016 Experimental and molecular medicine Vol.48 No.-

TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients with certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such as cell viability, proliferation and cell cycle progression. TGFBR1 upregulation induced by TFAP2C also promoted cell motility and migration, leading to malignant development. We also found that PAK1 (p21 protein (Cdc42/Rac)-activated kinase 1) signaling was involved in TFAP2C/ TGFBR1-induced tumorigenesis. These results were confirmed by an in vivo xenograft model and patient tissue samples. This study shows that TFAP2C promoted tumor progression by upregulation of TGFBR1 and consequent activation of PAK1 signaling.

가미소요산가자하차(加味逍遙散加紫河車)가 란소적출(卵巢摘出)로 유발(誘發)된 흰쥐의 골다공증(骨多孔症)에 미치는 영향(影響)

김완연 ( Wan Yeong Kim ),이인선 ( In Seon Lee ),소경순 ( Kyung Sun Soh ) 대한한의학회 한방재활의학과학회 2001 한방재활의학과학회지 Vol.11 No.4

Model Systems in Radiation Biology; Implication for Preclinical Study of Radiotherapy

Wanyeon Kim(김완연),Ki Moon Seong(성기문),Hee Jung Yang(양희정),HyeSook Youn(윤혜숙),BuHyun Youn(윤부현) 한국생명과학회 2012 생명과학회지 Vol.22 No.11

방사선 생물학에서 방사선에 대한 반응으로 매개되는 다양한 기작에 대한 분석을 위해 여러 종류의 모델 생물체를 사용해 왔다. 모델 생물체는 생물학적으로 온전한 in vivo 환경을 제공할 수 있기 때문에 방사선에 의해 발생되는 세포 내 현상은 물론 생리적인 현상이나 병리학적인 현상을 규명하는 데 있어서 모델 생물체를 사용하는 것은 효과적인 방법이 될 수 있다. 지금까지 축적된, 모델 생물체를 이용한 방사선 생물학적 연구결과들은 새로운 방사선치료 보조제의 개발, 방사선치료 효율 증진 등에 적용되어 여러 질병에 대한 임상연구의 기초가 되어왔다. 이렇게 유용하게 사용된 여러 모델 생물체에 있어서, 각각의 모델에 대한 개별적인 정보에 대한 연구는 다양한 방면에서 이루어지고 있지만, 통합적인 비교, 분석 및 정리를 한 경우는 부족한 실정이다. 따라서, 본 논문에서는 방사선 생물학에서 지금까지 많이 사용된 모델 생물체 4종(효모, 예쁜꼬마선충, 초파리, 생쥐)에 대해 각 생물체가 갖는 모델로써의 특징과 장단점 그리고 방사선 생물학 연구에 이용된 사례 등을 서술하고자 한다. In radiation biology, analysis of various mechanisms in response to radiation has been accomplished with the use of model organisms. These model organisms are powerful tools for providing a biologically intact in vivo environment to assess physiological and pathophysiological processes affected by radiation. Accumulated data using these models have been applied to human clinical studies (including the evaluation of radiotherapeutic efficacy) and discovery of radiotherapy reagents. However, there are few studies to provide overall integrated information about these useful model organisms. Thus, this review summarizes the results of radiation biology studies using four well-known model organisms: yeast, Caenorhabditis elegans, Drosophila melanogaster, and mice.

Roles of Oncogenic Long Non-coding RNAs in Cancer Development

도현희,김완연 한국유전체학회 2018 Genomics & informatics Vol.16 No.4

Long non-coding RNAs (lncRNAs) are classified as RNAs that are longer than 200 nucleotides and cannot be translated into protein. Several studies have demonstrated that lncRNAs are directly or indirectly involved in a variety of biological processes and in the regulation of gene expression. In addition, lncRNAs have important roles in many diseases including cancer. It has been shown that abnormal expression of lncRNAs is observed in several human solid tumors. Several studies have shown that many lncRNAs can function as oncogenes in cancer development through the induction of cell cycle progression, cell proliferation and invasion, anti-apoptosis, and metastasis. Oncogenic lncRNAs have the potential to become promising biomarkers and might be potent prognostic targets in cancer therapy. However, the biological and molecular mechanisms of lncRNA involvement in tumorigenesis have not yet been fully elucidated. This review summarizes studies on the regulatory and functional roles of oncogenic lncRNAs in the development and progression of various types of cancer.

Long non-coding RNA in glioma: novel genetic players in temozolomide resistance

노정욱,임미정,강지훈,윤부현,김완연 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

Glioma is the most common primary malignant brain tumor in adults and accounts forapproximately 80% of brain and central nervous system tumors. In 2021, the World HealthOrganization (WHO) published a new taxonomy for glioma based on its histological featuresand molecular alterations. Isocitrate dehydrogenase (IDH) catalyzes the decarboxylation ofisocitrate, a critical metabolic reaction in energy generation in cells. Mutations in the IDH genesinterrupt cell differentiation and serve as molecular biomarkers that can be used to classifygliomas. For example, the mutant IDH is widely detected in low-grade gliomas, whereas thewild type is in high-grade ones, including glioblastomas. Long non-coding RNAs (lncRNAs) areepigenetically involved in gene expression and contribute to glioma development. Toinvestigate the potential use of lncRNAs as biomarkers, we examined lncRNA dysregulationdependent on the IDH mutation status. We found that several lncRNAs, namely, AL606760.2,H19, MALAT1, PVT1 and SBF2-AS1 may function as glioma risk factors, whereas AC068643.1,AC079228.1, DGCR5, FAM13A-AS1, HAR1A and WDFY3-AS2 may have protective effects. Notably, H19, MALAT1, PVT1, and SBF2-AS1 have been associated with temozolomide resistancein glioma patients. This review study suggests that targeting glioma-associated lncRNAs mightaid the treatment of glioma.

Hippo-YAP/TAZ pathway regulation: the crucial roles of lncRNAs in cancer

장원이,임미정,노정욱,강지훈,김완연 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

The Hippo signaling pathway is a conserved signaling pathway that regulates cell proliferation,apoptosis, and differentiation and plays essential roles in the maintenance of organ size andtissue homeostasis. Also, this signaling pathway is a critical regulator of malignant progressionin a wide range of cancers. Furthermore, it has been established that YAP and TAZ are majoreffectors of the Hippo signaling pathway and transcription co-activators that regulate theexpressions of genes involved in cell growth and differentiation. Long non-coding RNAs(lncRNAs) are transcripts longer than 200 nucleotides involved in several biological processes,including chromatin remodeling, transcriptional regulation, and post-transcriptional processing. Evidence suggests that the aberrant expression and dysregulation of lncRNAs contribute to thedevelopment and progression of various malignancies by acting as oncogenes or tumorsuppressors. In addition, many studies have shown that lncRNAs can directly or indirectlyregulate the Hippo-YAP/TAZ signaling pathway in cancer. Here, we overview the roles played bylncRNAs in tumor progression with focus on their regulation of the Hippo-YAP/TAZ signalingpathway and discuss their potential usages as clinical biomarkers and therapeutic targets.

카페인 대사 유전자의 SNP를 활용한 RFLP 실험 프로그램 개발 및 적용

엄지수,노정욱,임지아,박지영,김은지,김완연 한국현장과학교육학회 2023 현장과학교육 Vol.17 No.3

In this study, we developed a molecular biology program focused on the CYP1A2 gene SNP, which is related to caffeine metabolism. This program was applied to high school students to assess changes in gene-related concept learning, scientific core competencies, and scientific attitudes. Thirty-six 2nd grade students from a general high school in Chungcheongbuk-do participated. They were divided into an experimental group (18 students) and a control group (18 students). The developed program was applied to the experimental group while the control group engaged in data analysis and activity-based lessons with the same content as the experimental group. The classes covered DNA extraction, gene amplification, enzyme processing, and DNA electrophoresis. Pre- and post-class assessments were conducted to analyze program's effectiveness. The result indicated that both the control group and the experimental group showed improvements in scientific core competencies, attitudes toward science, and conceptual understanding of molecular biology experiments. However, upon comparing the degree of improvement between the two groups, it was confirmed that the experimental group showed more positive enhancements in scientific core competencies, as well as conceptual understanding of molecular biology experiments, compared to the control group. Therefore, it is expected that the RFLP experiment program utilizing the SNP of the caffeine-metabolic gene will aid in enhancing general high school students' scientific core competencies, scientific attitude, and conceptual achievement related to molecular biology experiments.

High Yield Bacterial Expression and Purification of Active Cytochrome P450 p-coumarate-3-hydroxylase (C3H), the Arabidopsis Membrane Protein

Hee Jung Yang(양희정),Wanyeon Kim(김완연),Young Ju Yun(윤영주),Ji Won Yoon(윤지원),TaeWoo Kwon(권태우),HyeSook Youn(윤혜숙),BuHyun Youn(윤부현) 한국생명과학회 2009 생명과학회지 Vol.19 No.8

다양한 천연물의 합성대사에 관여하는 식물 cytochrome P450 (P450s)은 그 기능적 다양성에도 불구하고, 이들 효소의 광범위한 기질 특이성을 설명해 줄 수 있는 구조분석에 대해서는 충분한 연구가 이루어지지 못하고 있는 실정이다. 식물 p-coumarate 3-hydroxylase (C3H)에 의해 매개되는 효소 반응은 lignin 과 다양한 phenylpropanoid 부산물들의 생합성에 매우 중요한 것으로 여겨지지만, 막 단백질인 C3H의 발현 및 정제가 효과적으로 이루어지지 못하여, 활성을 측정하기 위한 분석방법이 체계화 되지 못하고 있다. C3H의 작용기작과 기질특이성에 대해 폭넓은 이해를 위한 구조분석의 선행단계는 활성을 갖는 C3H를 밀리그램 단위로 분리, 정제하는 실험적 방법을 확립하는 것이라 할 수 있다. 이를 위해, 본 연구에서는 다양한 돌연변이 방법을 도입하여 식물 막단백질 C3H를 대장균 시스템에서 효과적으로 발현 및 정제할 수 있는 시스템을 사용하였다. 변형된 cytochrome P450 C3H (C3Hmod)을 세포막으로부터 고농도의 염완충용액을 이용하여 계면활성제 없이 추출하였으며, 2단계 chromatography를 통해 활성을 유지한 상태로 분리할 수 있었다. 이러한 실험적 기법은 NMR 및 X-ray crystallography와 같은 구조분석을 통한 C3H의 효과적인 분석에 적용될 수 있을 것이며, 또한 다른 식물 cytochrome P450 단백질의 효과적인 분석에도 적용 될 수 있을 것이다. The cytochrome P450s (P450s) metabolizing natural products are among the most versatile biological catalysts known in plants, but knowledge of the structural basis for their broad substrate specificity has been limited. The activity of p-coumarate 3-hydroxylase (C3H) is thought to be essential for the biosynthesis of lignin and many other phenylpropanoid pathway products in plants however, all attempts to express and purify the protein corresponding C3H gene have failed. As a result, no conditions suitable for the unambiguous assay of the enzyme are known. The detailed understanding of the mechanism and substrate-specificity of C3Hdemands a method for the production of active protein on the milligram scale. We have developed a bacterial expression and purification system for the plant C3H, which allows for the quick expression and purification of active wild-type C3H via introduction of combinational mutagenesis. The modified cytochrome P450 C3H (C3Hmod) could be purified in the absence of detergent using immobilized metal affinity chromatography and size exclusion chromatography following extraction from isolated membranes in a high salt buffer and catalytically activated. This method makes the use of isotopic labeling of C3H for NMRstudies and X-ray crystallography practical, and is also applicable to other plant cytochrome P450 proteins.