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.

Effect of Elastic Compression Stocking and Kinesio Taping during Heel-raise Exercise on Muscle Activity, Mechanical Properties, and Muscle Fatigue in Healthy Women

윤성호,강윤정,김지현,도현희,신서영,이수빈,권중원 대한물리치료학회 2023 대한물리치료학회지 Vol.35 No.1

Purpose: The purpose of this study was to investigate the effectiveness of the elastic compression stockings and Kinesio taping on muscle activity and mechanical properties in healthy women during the heel raise exercise that causes muscle fatigue. Methods: Participants were divided into the elastic compression stockings group (ESG, n=8), Kinesio taping group (KTG, n=8), and control group (CG, n=8). All participants performed the heel raise exercise to cause muscle fatigue. Muscle activity, stiffness, and the muscle tone of the gastrocnemius and tibialis anterior were measured before and after the heel raise exercise. Results: In the gastrocnemius, muscle activity was significantly increased after the heel raise exercise in both the ESG and KTG (p<0.05). There was a significant difference in the change in the gastrocnemius muscle activity between the groups (p<0.05). Post hoc analysis showed that the ESG exhibited a significantly greater change in gastrocnemius muscle activity than the CG (p<0.05). The muscle stiffness of the gastrocnemius was significantly decreased after the heel raise exercise in the ESG (p<0.05). The muscle tone of the gastrocnemius was significantly increased after the heel raise exercise in the control group (p<0.05). There were no significant differences in the change in the gastrocnemius stiffness and muscle tone between the groups (p>0.05). In the tibialis anterior, there were no significant differences in muscle activity, stiffness, and muscle tone between and within the groups (p>0.05). Conclusion: Our findings suggest that the use of elastic compression stockings and Kinesio taping during the heel raise exercise are beneficial and delay muscle fatigue in the gastrocnemius.

TFAP2C Promotes Cell Proliferation by Upregulating CDC20 and TRIB3 in Non-small Cell Lung Cancer Cells

Dain Kim(김다인),Hyunhee Do(도현희),JiHoon Kang(강지훈),BuHyun Youn(윤부현),Wanyeon Kim(김완연) 한국생명과학회 2019 생명과학회지 Vol.29 No.6

전세계적으로 폐암 발병율은 서서히 감소하는 추세이지만, 여전히 암 관련 사망의 주요 원인으로 지목되고 있으며, 이에 따라 폐암 진단과 치료를 위한 새로운 분자적 지표를 발굴하는 연구가 활발히 이루어지고 있다. 본 연구진이 수행한 기존 연구에 따르면 폐암 환자에게서는 전사인자 중 하나인 TFAP2C가 높은 비율로 발현되며, 이 전사인자를 통해 폐암 발달에 상당한 영향을 끼치는 것을 확인할 수 있었다. TFAP2C는 다른 유전자들의 발현을 조절하여 암 형성에 기여하게 된다. 마이크로어레이 분석을 통해 TFAP2C에 의해 발현양이 조절되는 잠재적 표적 유전자들을 확인하였고, 특히 TFAP2C siRNA를 처리하였을 때 발현이 감소되는 원암유전자들 중 CDC20과 TRIB3 유전자를 최종적으로 선별하였다. 리얼타임 qRT-PCR과 웨스턴블롯을 통하여 두 유전자가 TFAP2C에 의존적으로 발현됨을 확인하였으며, 세포 생존 분석법을 통하여 CDC20과 TRIB3의 발현 증가가 폐암세포의 세포 증식을 유의미하게 유도하는 것을 확인하였다. 이와 더불어, CDC20과 TRIB3의 과발현이 폐암세포의 세포사멸 수준을 감소시켜 폐암 형성에 관여함을 확인하였다. 본 연구를 통하여 CDC20과 TRIB3가 폐암 형성을 유도할 수 있는 잠재적인 원암유전자로 기능함을 밝힐 수 있었으며, 두 유전자가 폐암 진단을 위한 표적유전자로서의 역할을 수행할 수 있을 것으로 기대한다. Non-small cell lung cancer (NSCLC) has the infamous distinction of being the leading cause of global cancer-related death over the past decade, and novel molecular targets are urgently required to change this status. We previously conducted a microarray analysis to investigate the association of transcription factor activating enhancer-binding protein 2C (TFAP2C) with NSCLC and revealed its oncogenic roles in NSCLC development. In this study, to identify new biomarkers for NSCLC, we focused on several oncogenes from the microarray analysis that are transcriptionally regulated by TFAP2C. Here, the cell division cycle 20 (CDC20) and tribbles pseudokinase 3 (TRIB3) were subsequently found as potential potent oncogenes as they are positively regulated by TFAP2C. The results showed that the mRNA and protein levels of CDC20 and TRIB3 were down-regulated in two NSCLC cell lines (NCI-H292 and NCI-H838), which were treated with TFAP2C siRNA, and that the overexpression of either CDC20 or TRIB3 was responsible for promoting cell viability in both NSCLC cell lines. In addition, apoptotic levels of NCI-H292 and NCI-H838 cells treated with TFAP2C siRNA were found to be suppressed by the overexpression of either CDC20 or TRIB3. Together, these results suggest that CDC20 and TRIB3 are positively related to NSCLC tumorigenesis and that they should be considered as potential prognostic markers for developing an NSCLC therapy.

Circadian Clock Genes, PER1 and PER2, as Tumor Suppressors

Beomseok Son(손범석),Hyunhee Do(도현희),EunGi Kim(김은기),BuHyun Youn(윤부현),Wanyeon Kim(김완연) 한국생명과학회 2017 생명과학회지 Vol.27 No.10

암을 포함한 다양한 인간의 질병 발생이 circadian clock 유전자의 변형된 발현 양상과 깊은 연관관계를 나타내고 있다. 세포 주기와 세포 성장은 circadian rhythm과 연결되어 있으며, 이를 조절하는 clock 유전자의 비정상적인 발현은 결국 종양 발생과 암의 발달을 유발하게 된다. Circadian clock에 관한 분자적 기전은 다수의 clock activator와 clock repressor의 통합적인 조절에 따른 전사 및 번역이 포함된 음성피드백 고리로 구성되어 있다. 이러한 circadian rhythm의 자동조절 기전에 의해 전체 유전체의 약 10~15%가 전사 수준에서 영향받는 것으로 나타났다. 많은 clock 유전자들 중, Period 1 (Per1)과 Period 2 (Per2)는 clock repressor 유전자로 정상적인 생리적 리듬을 조절하는 것에 기여한다. PER1과 PER2는 cyclin, CDK, CKI를 포함하는 세포 주기 조절자의 발현에 관여함이 밝혀졌으며, 다양한 암에서 PER1과 PER2의 발현 감소가 보고되었다. 따라서, 본 논문에서는 PER1과 PER2의 circadian rhythm에서의 분자적 기능과 종양 발생과 관련된 PER1과 PER2의 하위 표적인자에 대해 살펴보고, 암 치료를 위한 새로운 치료 표적과 암의 예후를 예측하기 위한 분자 지표로써의 PER1과 PER2의 가능성에 대해 서술하고자 한다. Disruptive expression patterns of the circadian clock genes are highly associated with many human diseases, including cancer. Cell cycle and proliferation is linked to a circadian rhythm; therefore, abnormal clock gene expression could result in tumorigenesis and malignant development. The molecular network of the circadian clock is based on transcriptional and translational feedback loops orchestrated by a variety of clock activators and clock repressors. The expression of 10~15% of the genome is controlled by the overall balance of circadian oscillation. Among the many clock genes, Period 1 (Per1) and Period 2 (Per2) are clock repressor genes that play an important role in the regulation of normal physiological rhythms. It has been reported that PER1 and PER2 are involved in the expression of cell cycle regulators including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. In addition, correlation of the down-regulation of PER1 and PER2 with development of many cancer types has been revealed. In this review, we focused on the molecular function of PER1 and PER2 in the circadian clock network and the transcriptional and translational targets of PER1 and PER2 involved in cell cycle and tumorigenesis. Moreover, we provide information suggesting that PER1 and PER2 could be promising therapeutic targets for cancer therapies and serve as potential prognostic markers for certain types of human cancers.

니코틴 의존도 평가검사로서 Heavy Smoking Index (HSI)의 유용성

이성기,김경래,최재경,조희경,조동영,권혁중,임대준,모현희,도현희,오승원,임열리 대한가정의학회 2008 Korean Journal of Family Medicine Vol.29 No.6

The Usefulness of Heavy Smoking Index as a Test for Nicotine DependenceSung Ki Lee, M.D., Hyuk Jung Kweon, M.D., Dae Jun Lim, M.D.*, Kyong Rae Kim, M.D.**, Hyun Hee Mo, M.D.***, Hyun Jin Do, M.D., Seung Won Oh, M.D., Youl Lee Lym, M.D., Jae Kyung Choi, M.D., Hee Kyung Joh, M.D., Dong Yung Cho, M.D. Background: The Fagerstrom Test for Nicotine Dependence (FTND) is a widely used six-item questionnaire. Its completion require a few minutes, but such time may be too much for busy clinicians and large epidemiologic surveys. The goals of this study was to compare the sensitivity and the specificity of Heavy Smoking Index (HSI) of high nicotine dependence. Methods: The FTND was administered to 943 current smokers from a smoking-cessation clinic in Gwangjin-gu, Seoul. The HSI which combines two items of the FTND (the number of cigarettes per day and the time of the first cigarette of the day) was compared to the FTND. We measured cigarette per day, duration of smoking, and age of smoking initiation. Results: A cutoff score equal or greater than 4 on the HSI detected a similar rate of nicotine dependence as a cutoff score equal or greater than 6 on the FTND. The HSI showed a sensitivity of 88.0% and a specificity of 86.5%. The concordance between the two instruments was high (kappa= 0.74). Conclusion: The HSI was proven to be very useful. If HSI had a proper validity, the HSI can be a good standard of high nicotine dependence for busy clinician and epidemiologists. (J Korean Acad Fam Med 2008;29:405-411) 연구배경: 니코틴 의존도를 평가하는데 널리 이용되는 Fagerstrom의 니코틴 의존도 설문지(Fagerstrom test of nicotine dependence, FTND)는 6개 설문으로 이루어져 있어, 외래환자나 대규모 역학조사 등에 일상적으로 적용하기엔 어려운 점이 있었다. 이에 FTND의 두 가지 설문항목으로 이루어진 Heavy smoking index (HSI)의 유용성과 흡연 관련인자와의 상관관계에 대해 알아보고자 하였다. 방법: 일개 보건소의 금연클리닉을 등록한 943명의 성인흡연자를 대상으로 하였다. FTND 한국어판 설문지를 이용하여 니코틴 의존도를 조사하고, FTND의 두가지 설문문항(하루 중 첫 담배를 피우는 시간, 하루 중 흡연량)으로 이루어진 HSI의 민감도, 특이도, FTND와의 일치도를 구하였다. 하루 중 평균 흡연량, 총 흡연기간, 첫 흡연시작시기를 조사하여 상관관계를 알아보았다. 결과: FTND 총점 6점 이상을 기준으로, HSI 4점 이상인 경우 두 측정방식 사이의 일치도는 높았다(kappa=0.74). HSI의 민감도는 88.0%이고 특이도는 86.5%였다. 결론: HSI의 유용성은 높았고, 타당도가 검증되면 외래진료에서 간편하고 비교적 정확하게 니코틴 의존도를 예측할 수 있는 척도로서 활용될 수 있다.