miR-210 Regulates Apoptotic Cell Death during Cellular Hypoxia and Reoxygenation in a Diametrically Opposite Manner
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Abstract:
Apoptotic cell death of cardiomyocytes is a characteristic hallmark of ischemia-reperfusion (I/R) injury. The masterKeywords:
Hypoxia
bcl-2 암유전자는 여러 가지 자극에 의한 apoptosis를 차단함으로써 유전자 이상을 가진 세포가 계속 생존하면서 유전자 변이가 누적되는 결과를 초래한다고 알려져 있다. 한편 c-myc 암유전자는 세포증식과 apoptosis를 유도하는 이중적 기능을 가지고 있으며 생존 신호가 결여될 경우에는 오히려 세포의 apoptosis를 유발한다고 알려져 있다. 그러나 c-myc과 bcl-2가 동시에 발현되면 bcl-2는 c-myc의 세포증식 작용은 영향을 주지 않고 apoptosis만을 선택적으로 차단함으로써 유전자 변이 세포의 생존 뿐만 아니라 증식을 촉진하는 것으로 관찰되었다. 자궁경부암에서 c-myc과 bcl-2 발현에 관한 개별적 보고는 있었으나 이들 두 유전자의 동시발현 및 이들 유전자들이 실제 암조직상에서 세포증식 및 apoptosis에 어떠한 영향을 미치는가에 관한 연구는 보고된 것이 없다. 따라서 본 연구에서는 자궁경부암 발생 과정중에서 bcl-2 및 c-myc 발현과 세포증식, apoptosis와의 상관관계를 알아보고자 하였다. 본 연구에서는 10개의 정상 자궁경부조직, 30개의 자궁경부 상피내종양 조직, 20개의 자궁경부암조직에서 bcl-2와 c-myc에 대한 면역조직화학 검사를 시행하였으며 세포증식과 apoptosis는 각각 Ki-67 면역조직화학적 방법과 TUNEL 방법으로 확인하였다. 또한 환자의 임상병리학적 인자들과의 상관관계도 알아보았다. 정상 자궁경부, 자궁경부 상피내종양, 자궁경부암조직 중 자궁경부암조직에서만 bcl-2와 c-myc 단백이 각각 35%와 50%에서 관찰되었으며, 또한 bcl-2와 c-myc의 동시발현이 25%에서 관찰되었다. 세포증식 지수(상피세포 100개중 Ki-67양성 세포수)는 정상 자궁경부, 상피내종양, 자궁경부암으로 진행되면서 10.2, 24.1, 59.7, 71.2로 유의하게 증가하는 양상을 보였으며(p<0.01), apoptosis 지수(상피세포 100개중 apoptosis 세포수)도 0, 0.33, 1.85, 3.89로 점차 증가하는 양상을 보였다(p<0.01). 또한 세포증식 지수와 apoptosis 지수와는 높은 상관관계(r=0.7451, p=0.0002)를 나타내었다. 그러나 자궁경부암 조직중 bcl-2 발현군과 비발현군간에 apoptosis지수에는 차이가 없었으며(p=0.4765), c-myc 발현군과 비발현군간에도 세포증식 지수에는 차이가 없었다(p=0.6891). 또한 bcl-2와 c-myc의 동시 발현군과 나머지 군간에도 증식지수와 apoptosis 지수에 차이가 없었다(각각 p=0.6311 및 p=0.7600). 한편 bcl-2와 c-myc의 동시 발현과 잘 알려져 있는 자궁경부암의 임상병리학적 예후인자들(종양 크기, FIGO 임상병기, 림프절 전이등)과는 유의한 상관관계가 없었다. 이상과 같은 결과에서 자궁경부암발생 과정에서 세포증식과 apoptosis는 병변의 등급과 비례하여 증가하고 apoptosis는 세포증식과 관련된 변화로 사료되었다. 한편 bcl-2와 c-myc과 발현은 자궁경부암에서만 관찰되는 유전자 변이로서 자궁경부 상피내종양의 발생과 진행과정에는 영향을 미치지 않으며, 또한 자궁경부암 조직에서도 암조직 전체의 세포증식 및 apoptosis와는 관련이 없을 것으로 사료되었다.
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目的．microRNA（miRNA）は約22塩基のnon-coding RNAで標的遺伝子の発現を抑制し，発生·分化の制御など種々の生物学的機能を果たしている．我々は肺癌に於けるmiRNAの異常と，肺癌の発症·進展への関与を検討した．研究計画．癌に関連する可能性が考えられるmiRNA群を選択し，正常肺·肺癌検体におけるmiRNAの発現を比較検討した．また，miRNAやアンチセンスオリゴを細胞内導入し，miRNAの機能を検討した．結果．let-7ファミリーが肺癌で高頻度に発現低下し，その発現低下が予後不良因子であることが判明した．また，miR-17-92クラスターの過剰発現が見出された．このmiR-17-92クラスターの強制発現で増殖促進が見られ，一方，アンチセンスオリゴによる発現抑制が，miR-17-92クラスターを強発現している肺癌細胞株特異的に増殖抑制·細胞死誘導を引き起こした．結論．let-7ファミリーが癌抑制遺伝子として，また，miR-17-92クラスターが癌遺伝子として機能しており，これらmiRNAの異常が，肺癌の発症·進展に深く関与することが示唆された．他のmiRNAの癌への関与も報告され，今後miRNA発現解析の癌の診断·予後予測への応用や，miRNAを用いた治療·miRNAを標的とする治療などの開発が期待される．
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Hypoxia
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瞄准：学习是否消炎痛(IND )(NS ) ，一个非选择的 cyclooxygenase (艇长) 禁止者或 NS-398，一个 COX-2-selective 禁止者，在人的结肠癌房间导致 apoptosis 并且 apoptosis 相关的基因和小径它被包含。方法：人的结肠癌 Caco-2 房间与也被对待：安慰剂， IND (0.05-0.5 mmol/L ) 或为 1， 5 和 18 h 的 NS (0.01-0.2 mmol/L ) 。我们然后学习了：(1 ) 由 TUNEL 方法的细胞死亡，(2 ) 用 DNA 微数组的 96 apoptosis 相关的基因的 mRNA 表示，(3 ) 选择 apoptosis 的表示由西方的弄污联系了蛋白质。结果：IND 和 NS 以一种剂量依赖者方式在 Caco-2 房间的 30%-50% 导致了 apoptosis。IND (为 1 h 的 0.1 mmol/L ) 在四个家庭的显著地起来调整的 pro-apoptotic 基因：(1 ) TNF 受体和 ligand，(2 ) Caspase，(3 ) Bcl-2 并且(4 ) Caspase 招募领域。NS 治疗起来调整的类似的 pro-apoptotic 基因作为 IND。另外，国际机场家庭的 IND 也下面调整的 anti-apoptotic 基因。结论：(1 ) 非选择并且在以一种剂量依赖者方式的结肠癌房间的 COX-2-selective NSAID induce apoptosis。(2 ) 两 NSAID 由激活二条主要 apoptotic 小径导致 apoptosis：死亡受体小径(包含的 TNF-R ) 和 mitochondrial 小径。(3 ) IND 由起来调整的 pro-apoptotic 基因和下面调整的 anti-apoptotic 基因导致 apoptosis，当时 NS 仅仅起来调整 pro-apoptotic 基因。(4 ) 在由 NSAID 的结肠癌房间的 apoptosis 的正式就职可以部分地解释，他们结肠癌生长上的禁止的行动。
Caspase 8
Intrinsic apoptosis
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目的将开始由微数组技术在人的胰腺的癌症房间线分析 miRNAs 表示侧面的差别。743 根探针全部的方法 A 根据人，老鼠，和老鼠的已知的 miRNAs 序列被设计。miRNAs 微数组被生产，它的可靠被验证。全部的 RNA 被提取， miRNAs 与胰腺的癌症房间衬里的人(SW1990， Capan-2， BxPC-3， Aspc-1，和 Panc1 ) 和不朽的人被分开胰腺的管上皮的房间线 H6C7。他们用 T4 RNA ligase 被标记，当时是有微数组的 hybridized。通过数组扫描和分析，在胰腺的癌症的 miRNAs 表达式侧面被获得。结果被北弄污和 RT-PCR 验证。与胰腺的癌症有关的 63 miRNAs 全部的结果 A 被发现是在 5 根胰腺的癌症房间线表示的差别，包括 25 下面调整并且 38 起来调整的 miRNAs。mir-21 和 let-7 的表情也被证实。结果建议了侧面能在胰腺的癌症房间被发现的那 miRNAs 表情的结论。
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AIM: To compare hypoxia and hypoxia reoxygenation induced apoptosis of cardiomyocytes and to investigate the role of apoptosis in cardiomyocytes injury caused by hypoxia/reoxygenation. METHODS: Cultured neonatal rat cardiomyocytes were divided into two groups.Both groups were cultured in an incubator of 950 ml/L N 2 and 50 ml/L CO 2 for 16, 32 and 48 h. Cells of one group were put into normal incubation for 6 h after hypoxia to form the cell models of hypoxia reoxygenation injury. Morphological changes in apoptotic cardiomyocytes were measured by TUNEL staining. Apoptosis rates were measured by flow cytometer. RESULTS: Positive cells were detected by TUNEL staining. Apoptotis rates of cardiomyocytes measured by flow cytometer after hypoxia for 16,32 and 48 h were (2.9±0.5)%,(6.2±0.8)% and (26.6±3 0)% respectively.The apoptosis rates of cells undergoing hypoxia for 16,32 and 48 h followed by reoxygenation for 6 h were (5.5±0.7)%,(11.0±1.1)% and (14.2±1.6)% respectively. CONCLUSION: The apoptosis rates of cardiomyocytes increased with time of hypoxia.Reoxygenation could worsen cardiomyocytes injury,as compared with hypoxia.
Hypoxia
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MicroRNAs are well-known strong RNA regulators modulating whole functional units in complex signaling networks. Regarding clinical application, they have potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21 promotes and microRNA-34 inhibits cancer progression. We elucidate here involved pathways and imbed these antagonistic microRNAs in a network of interactions, stressing their cancer microRNA biology, followed by experimental and bioinformatics analysis of such microRNAs and their targets. This background is then illuminated from a clinical perspective on microRNA-21 and microRNA-34 as general examples for the complex microRNA biology in lung cancer and its diagnostic value. Moreover, we discuss the immense potential that microRNAs such as microRNA-21 and microRNA-34 imply by their broad regulatory effects. These should be explored for novel therapeutic strategies in the clinic.
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Purpose of the study . Determination of the expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 in colon tumor tissue depending on the clinical and morphological features of the tumor and the effectiveness of treatment. Materials and methods . The study included 56 patients diagnosed with colorectal cancer aged 43 to 75 years with the average age of 54 years. Taking into account the local prevalence of the process patients received surgical or combined treatment, including neoadjuvant chemotherapy, in the clinics of the Cancer Research Institute, Tomsk NRMC. MicroRNA expression was determined by polymerase chain reaction (PCR) in real time. Results . The obtained information revealed the relation of microRNA‑130 to the tumor size. The development of regional metastases was associated with changes in microRNA‑130, microRNA‑194 and microRNA‑605. The level of histological organization of the tumor was associated with microRNA‑34, microRNA‑130, microRNA‑148, and the response to therapy – with microRNA‑130, microRNA‑148 and microRNA‑605. In addition, according to the study, the significance of microRNA‑130 was revealed, which is associated with tumor spread, histological differentiation and response to antitumor therapy. Conclusion . The features of expression of microRNA‑34, microRNA‑130, microRNA‑148, microRNA‑181, microRNA‑194 and microRNA‑605 associated with clinical and morphological features of colon tumors were revealed. Correlations between the studied indicators are noted, which probably determine the outcome and prognosis of the disease.
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Aim To study the role of hypoxiainduced apoptosis in neonatal rat cardiomyocyte and the protection effect of nitric oxide(NO). Methods Neonatal rat cardiomyocytes were cultured in an incubator of 950 mL/L N 2 and 50 mL/L CO 2 for 16, 32 and 48 h to create cell models of hypoxia injury and detect apoptosis. And NO donor SNAP at 100 μ mol/L was added to the models. Apoptosis was detected in the hypoxia cells without or with No treatment. Results After hypoxia of 16, 32 and 48 h,the apoptosis rates of cardiomyocytes were 29% ± 05% , 62% ± 08% and 266% ± 30% , respectively. Whereas the apoptosis rates of cells treated with SNAP were 02% ± 03% , 34% ± 04% and 118% ± 12% , respectively. Conclusion Apoptosis is the main form of hypoxia injury in cardiomyocytes; NO protect cardiomyocytes from apoptosis induced by hypoxia.
Hypoxia
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