GPX7在甲状腺乳头状癌中的研究

发布时间：2018-04-29 11:58

本文选题：谷胱甘肽过氧化物酶 + 7　；参考：《大连医科大学》2017年博士论文

【摘要】：研究背景:甲状腺癌是内分泌器官中最常见的恶性肿瘤,主要病理类型有甲状腺乳头状癌(papillary thyroid carcinoma,PTC)、滤泡癌、未分化癌和髓样癌等。其中PTC最为常见。一般而言,PTC发展缓慢,病程较长,预后较好,但也有很多PTC患者因没有临床症状,就诊较晚,一经发现,即伴随有淋巴结转移、被膜侵犯等情况,导致患者的预后不佳;故仍需要早发现、早诊断、早治疗PTC。尽管多数文献报道,PTC的发病机制与BRAF基因突变、RET/PTC基因重排等有关,但目前有关PTC的发病机制仍未完全明确,因此深入研究PTC的发病机制有着重要的临床意义。哺乳动物细胞中的谷胱甘肽过氧化物酶(glutathione peroxidase,GPXs)是机体内最主要的氧化还原酶,由8种GPX组成,分别命名为GPX1-GPX8,其中GPX1-GPX4以及GPX6为含硒代半胱氨酸的GPXs,GPX5、GPX7及GPX8则为非含硒代半胱氨酸的GPXs。通常,含硒代半胱氨酸的GPXs能够通过催化还原型谷胱甘肽(GSH)来还原H2O2,以达到降低疾病氧化应激反应的作用。而非含硒代半胱氨酸的GPXs,不同于含硒代半胱氨酸的GPXs,其缺少GSH结合结构域,因此,它们引起过氧化物酶活性的机制还存在争议。活性氧簇(reactive oxygen species,ROS)包括氧离子和过氧化物等活性含氧分子,是机体正常代谢产生的内在产物。有学者提出氧化应激反应与肿瘤的发生、发展有关。所谓的氧化应激反应是指机体遭受有害刺激时,体内的ROS产生过多,使机体氧化程度超出氧化物的清除,使得氧化系统与抗氧化系统失衡而引起的组织损伤。ROS包括O2-、H2O2、HO2-、-OH等的活性含氧分子。长期持续的氧化应激,会导致自身免疫异常、肿瘤发生、糖尿病、肥胖、神经变性和衰老等等多种疾病。甲状腺的主要生理功能是合成甲状腺激素,其中的h2o2作为甲状腺激素合成的关键酶-甲状腺过氧化物酶的必需底物,对甲状腺激素合成及发挥正常甲状腺生理功能起到非常重要的作用。当机体发生异常时,h2o2可在甲状腺中过度蓄积,使得甲状腺持续暴露在高浓度的h2o2及其附带效应产生的ros环境中,即氧化应激反应中,使甲状腺细胞受到氧化性dna损伤或基因低甲基化。已有研究证实,大量的ros可促进自身细胞的增殖、侵袭、转移及血管生成,并能逃避凋亡的发生。因此,氧化还原反应的异常可能与ptc的发生、发展有关。gpx7是gpxs家族成员之一,主要参与维持机体的氧化还原稳态的作用。近年来研究发现,gpx7异常表达与多种肿瘤(包括食管腺癌、乳腺癌、肝细胞癌等)的发生、发展相关,但有关gpx7在甲状腺癌中的研究尚未见报道。已知nf-κb是一种存在于真核细胞中控制dna转录的重要核转录因子,具有多向转录调节作用,已证实nf-κb与多种恶性肿瘤的发生、发展有关。有文献报道gpx7在食管腺癌(eac)中的作用有可能是通过nf-κb信号通路来发挥作用的。cyclind1能够正性调控细胞周期,是检测细胞增殖活性的指标之一,有报道cyclind1是nf-κbp65的重要下游靶基因。有关gpx7在甲状腺乳头状癌中与nf-κb、cyclind1表达关系的研究,尚未见报道。因此,本研究目的是从组织和细胞水平分别研究gpx7在ptc中的表达,以及与ptc临床病理参数的关系,探讨gpx7在ptc发生、发展过程中的作用及可能机制,为进一步研究gpx7在甲状腺乳头状癌中的作用机制奠定基础。目的:1、从组织和细胞水平研究gpx7在ptc中的表达情况及对ptc细胞增殖和凋亡的影响,探讨gpx7在ptc发生、发展中所起的作用。2、从组织和细胞水平分别研究gpx7与nf-κbp65、cyclind1表达的关系,探讨gpx7参与调控ptc细胞增殖与凋亡的可能机制。3、研究gpx7蛋白在伴有桥本甲状腺炎的甲状腺乳头状癌(ptc+ht)组织中的表达,探讨桥本甲状腺炎的炎性微环境对gpx7表达的影响,为进一步研究gpx7在甲状腺乳头状癌中的作用机制奠定基础。方法:1、用免疫组织化学方法检测30例ptc、14例结节性甲状腺肿(结甲)组织中gpx7蛋白的表达情况,并分析gpx7与临床病理特征的关系。2、构建gpx7基因干扰慢病毒载体,用westernblot方法外源验证靶点有效后,用构建成功的gpx7基因干扰慢病毒载体感染甲状腺乳头状癌(k1)细胞,使用qt-pcr的方法检测基因敲减效果;并用多种细胞功能实验(celigo细胞计数、流式细胞仪检测、caspase3/7检测、mtt检测、细胞克隆形成实验)方法,观察gpx7基因敲减与未基因敲减的k1细胞的细胞增殖、凋亡、克隆形成的差异。3、用免疫组织化学方法检测30例ptc、14例结节性甲状腺肿(结甲)组织中nf-κbp65、cyclind1蛋白的表达情况,分析各指标与gpx7表达的关系。4、用gpx7基因干扰慢病毒载体感染k1细胞,并用westernblot方法检测gpx7基因敲减前后nf-κbp65、cyclind1蛋白表达情况。5、用免疫组织化学方法检测29例伴有桥本甲状腺炎的甲状腺乳头状癌(ptc+ht组)、31例甲状腺乳头状癌(ptc组)、16例桥本甲状腺炎(ht组)以及14例结节性甲状腺肿(结甲组)组织的gpx7表达情况,结合临床病理参数,探讨桥本甲状腺炎的炎性微环境对gpx7表达的影响及在甲状腺乳头状癌中所起的作用。6、免疫组化评判标准:每例均随机观察5个高倍视野,根据染色细胞百分率和染色强度进行评定和分析。阳性细胞百分率计分标准:10%为0分,11%~25%为1分,26%~50%为2分,51%~75%为3分,75%为4分;染色强度计分:无染色为0分,浅黄色为1分,棕黄色为2分,棕褐色为3分。将阳性细胞率得分和染色强度得分相乘即为最后得分,0分为阴性(-),1~4分为弱阳性(+),5~8分为中度阳性(++),9~12分为强阳性(+++)。7、统计学方法:采用spss20.0统计软件进行统计分析,计量资料采用均数±标准差表示,组间差异比较采用独立样本t检验,如方差不齐则采用t’检验。计数资料采用例(百分率)表示,组间比较采用卡方检验。相关性分析采用pearson相关性分析。p0.05为差异具有统计学意义。结果:1、gpx7对甲状腺乳头状癌细胞增殖、凋亡影响的研究(1)免疫组化结果:(1)gpx7表达于甲状腺细胞胞质中。gpx7在ptc组表达阳性率为100.0%,以中-强阳性为主;结甲组gpx7表达表达阳性率为30.0%,以弱阳性为主,ptc组gpx7表达明显高于结甲组(p0.05)。(2)gpx7的表达与肿瘤最大径呈正相关关系(r=0.601,p0.05),且gpx7高表达组肿瘤最大径(1.56±0.56cm)明显大于gpx7低表达组(0.56±0.13cm)(p0.05)。(2)细胞实验结果:(1)选取两种人甲状腺乳头状癌细胞系tpc-1和k1。qt-pcr结果显示gpx7基因在tpc-1和k1细胞中都有较高的表达丰度。相比较k1细胞表达丰度更高,故选取k1细胞进行后续实验研究。(2)gpx7基因干扰慢病毒载体制备后,采用westernblot外源验证,发现gpx7基因敲减后gpx7的表达明显减少,说明靶点对gpx7基因的外源表达有敲减作用,是有效靶点。(3)gpx7基因干扰慢病毒载体感染k1细胞后通过普通显微镜和荧光显微镜下观察,发现细胞感染效率达到80%以上,且细胞状态正常,采用qpcr的法证实经shrna慢病毒感染后,k1细胞中gpx7基因在mrna水平的表达量受到抑制,敲减效率达到81.5%,说明载体感染k1细胞效果好,可以进行后续的实验观察。(4)celigo细胞计数结果显示,gpx7基因敲减组细胞增殖数明显减少,培养第5天较第1天仅增殖(5.00±0.32)倍,与对照组的(8.44±0.26)相比较,增殖速率明显减慢。(5)流式细胞仪检测发现,gpx7基因敲减组细胞凋亡百分比(24.08±0.28)%,与对照组的(4.33±0.15)%相比较,凋亡比例明显增多。(6)caspase3/7活性检测发现,gpx7基因敲减组的caspase3/7活性值为(257.82±21.28),与对照组的(100.00±5.38)相比较,明显增加。(7)mtt检测发现,gpx7基因敲减组培养第5天od490值较第1天增长(3.081±0.160)倍,与对照组(增长4.897±0.091倍)相比较,gpx7基因敲减组细胞增长倍数明显减少。(8)细胞克隆形成检测实验发现,gpx7基因敲减组克隆形成数(283±6)与对照组克隆形成数(710±10)相比较,明显减少。2、gpx7在甲状腺乳头状癌中的可能作用机制(1)免疫组化结果(1)nf-κbp65表达于甲状腺细胞胞质和(或)细胞核中。ptc组表达明显高于结甲组。ptc组nf-κbp65的阳性表达率达83.3%,以中度阳性为主。(2)cyclind1表达于甲状腺细胞核。ptc组表达明显高于结甲组。ptc组cyclind1阳性表达率达到96.7%,以中度阳性为主。(3)gpx7、nf-κbp65、cyclind1蛋白表达呈显著正相关(r值分别为0.721、0.589、0.703,p值均0.05)。(4)ptc组gpx7与nf-κbp65联合检测阳性率为83.3%,与cyclind1联合检测阳性率为100.0%,三者联合检测阳性率为83.3%。(2)细胞实验结果(1)慢病毒感染目的细胞效率较高,qpcr证实gpx7基因被有效敲减。(2)westernblot实验结果显示,敲减甲状腺乳头状癌细胞(k1细胞系)的gpx7基因后,nf-κbp65蛋白表达量无明显变化,cyclind1蛋白表达量增高,与敲减前比较,差异有统计学意义(p0.05)。3、炎性微环境对gpx7在ptc中表达的影响结果(1)免疫组化结果显示,伴桥本甲状腺炎的甲状腺乳头状癌组织gpx7蛋白表达评分(6.21±2.29)低于甲状腺乳头状癌(8.52±2.41),差异有统计学意义(p0.05)。(2)单因素分析发现影响gpx7表达的因素有合并ht、tg-ab、tpo-ab、肿瘤部位和被膜侵犯情况,其中gpx7与合并ht、tg-ab和tpo-ab水平呈负相关,与肿瘤部位、被膜侵犯情况呈正相关。(3)多因素线性回归分析发现影响gpx7表达的因素为有合并ht。(4)临床病理特征分析,发现合并ht炎性环境的ptc肿瘤多局限于单侧,被膜侵犯发生率低。结论:1、免疫组化和细胞实验结果显示GPX7在甲状腺乳头状癌中高表达。2、免疫组化和细胞实验结果提示GPX7具有促进甲状腺乳头状癌细胞增殖、减少细胞凋亡的作用。3、GPX7、NF-κB p65、Cyclin D1蛋白在甲状腺乳头状癌中的表达呈正相关,提示三者在甲状腺乳头状癌的发生、发展中可能有关联。4、GPX7基因敲减后NF-κB p65蛋白表达无变化,提示GPX7对甲状腺乳头状癌的作用与NF-κB信号通路无关或不是通过调节其蛋白表达量来实现的。5、GPX7基因敲减后Cyclin D1蛋白表达增高,机制不清。6、通过单因素和多因素线性回归分析,发现是否合并桥本甲状腺炎是影响甲状腺乳头状癌组织中GPX7表达的因素,提示桥本甲状腺炎的炎性环境能抑制甲状腺乳头状癌组织中GPX7的表达。
[Abstract]:Background: thyroid cancer is the most common malignant tumor in the endocrine organs. The main pathological types are papillary thyroid carcinoma (PTC), follicular, undifferentiated and medullary carcinoma. Among them, PTC is the most common. Generally speaking, the development of PTC is slow, the course is longer, and the prognosis is better, but there are many PTC patients who have no presence. Bed symptoms, later diagnosis, once found, that is accompanied by lymph node metastasis, membrane invasion and other conditions, resulting in poor prognosis. Therefore, early detection, early diagnosis, early treatment of PTC., although most of the literature reports, the pathogenesis of PTC is related to the BRAF gene mutation, the RET/PTC gene rearrangement, but the pathogenesis of PTC is still not completely clear. It is true that it is important to study the pathogenesis of PTC. The glutathione peroxidase (GPXs) in mammalian cells is the most important oxidoreductase in the body, which is composed of 8 GPX, named GPX1-GPX8, and GPX1-GPX4 and GPX6 are GPXs, GPX5, GPX7, and selenocysteine containing selenocysteine. GPX8 is the GPXs. of non selenocysteine, and the selenocysteine containing GPXs can reduce H2O2 by catalyzing the reduced glutathione (GSH) to reduce the oxidative stress of the disease. The non selenocysteine GPXs, which is different from the selenocysteine containing GPXs, lacks the GSH binding domain. Therefore, they are lacking in the GSH binding domain. The mechanism that causes peroxidase activity is still controversial. Reactive oxygen species (ROS), which includes oxygen ions and peroxide and other active oxygen molecules, is an intrinsic product of the body's normal metabolism. Some scholars suggest that oxidative stress reaction is related to the occurrence and development of tumor. The so-called oxidative stress reaction refers to the body suffered. In the case of harmful stimulation, the ROS in the body produces too much to make the body oxidize beyond the oxide clearance, which causes the tissue damage caused by the imbalance of the oxidation system and the antioxidant system, including the active oxygen containing molecules of O2-, H2O2, HO2-, -OH and so on. Long-term persistent oxidative stress leads to autoimmune abnormalities, tumorigenesis, diabetes, obesity, and nerves. A variety of diseases such as degeneration and aging. The main physiological function of the thyroid gland is the synthesis of thyroid hormones. The H2O2, the key enzyme of the thyroid hormone synthesis, is essential to the thyroid peroxidase, which plays an unusually important role in the synthesis of thyroid hormones and the functioning of normal thyroid function. When the body is abnormal, H2O2 Excessive accumulation in the thyroid gland causes the thyroid to continue to expose to a high concentration of H2O2 and its incidental effect in the ROS environment, that is, oxidative stress in the oxidative stress response, causing oxidative DNA damage or hypomethylation of the thyroid cells. A large number of ROS have been confirmed to promote the proliferation, invasion, metastasis and angiogenesis of the cells of the cells. And it can escape the occurrence of apoptosis. Therefore, the abnormality of redox reaction may be associated with the occurrence of PTC, and the development of.Gpx7 is one of the members of the GPxs family, which is mainly involved in maintaining the redox homeostasis of the body. In recent years, the abnormal expression of gpx7 has been found to be associated with the development of a variety of tumors, including tubular adenocarcinoma, breast cancer, hepatocellular carcinoma and so on. However, the study of gpx7 in thyroid cancer has not yet been reported. It is known that nf- kappa B is an important nuclear transcription factor that exists in eukaryotic cells to control DNA transcription. It has a multidirectional transcriptional regulation. It has been confirmed that nf- kappa B is associated with the development of a variety of malignant tumors. It is reported that the role of gpx7 in the esophageal adenocarcinoma (EAC) is possible. It is one of the indicators for detecting cell proliferation activity by nf- kappa B signaling pathway, which is one of the indicators for detecting cell proliferation activity. It is reported that CyclinD1 is an important downstream target gene of nf- kappa bp65. The study of the relationship between gpx7 in thyroid papillary carcinoma and nf- kappa B, CyclinD1 expression has not been reported. Therefore, this study aims to study the purpose of this study. The expression of gpx7 in PTC, as well as the relationship with PTC clinicopathological parameters, and the role of gpx7 in the development of PTC and its possible mechanism are discussed, respectively, to further study the mechanism of gpx7 in the thyroid papillary carcinoma. Objective: 1, the study of gpx7 in PTC from the tissue and cell levels. The effect of expression and the effect on the proliferation and apoptosis of PTC cells and the role of gpx7 in the development of PTC,.2, the relationship between gpx7 and nf- kappa bp65, CyclinD1 expression from tissue and cell levels, and the possible mechanism of gpx7 participating in the regulation of proliferation and apoptosis of PTC cells, and the study of the gpx7 protein in the thyroid gland with Hashimoto's thyroiditis The expression in the tissue of papillary carcinoma (ptc+ht) and the influence of the inflammatory microenvironment of Hashimoto's thyroiditis on the expression of gpx7 in the thyroid papillary carcinoma are established. Methods: 1, the expression of gpx7 protein in 30 cases of PTC and 14 cases of nodular goiter (nail) was detected by immunohistochemistry. The relationship between gpx7 and clinicopathological features was analyzed, and.2 was used to construct the gpx7 gene to interfere with the lentivirus vector. After the target was validated by the Westernblot method, a successful gpx7 gene was used to infect the thyroid papillary carcinoma (K1) cells of the thyroid carcinoma (K1) cells, and the gene knockout effect was detected by the formula of qt-pcr, and a variety of cell functional experiments were used. (celigo cell count, flow cytometry, caspase3/7 detection, MTT detection, and cell clone formation experiment) to observe the proliferation, apoptosis, and clone formation of gpx7 gene knockout and non gene knockout K1 cells,.3, 30 cases of PTC, 14 cases of nodular goiter (thyroid gland), nf- kappa bp65, Cycli, and Cycli. The relationship between the expression of ND1 protein and the expression of gpx7 was analyzed.4, K1 cells were infected with the gpx7 gene to interfere with the lentivirus vector, and the nf- kappa bp65 before and after the gpx7 knockout was detected by Westernblot, and the expression of cyclinD1 protein was.5. 29 cases of thyroid papillary carcinoma with Hashimoto's thyroiditis were detected by immunohistochemistry (ptc+ht). The expression of gpx7 in 31 cases of thyroid papillary carcinoma (Group PTC), 16 cases of Hashimoto thyroiditis (Group HT) and 14 cases of nodular goiter (group A), combined with the clinicopathological parameters, the effects of the inflammatory microenvironment of Hashimoto's thyroiditis on the expression of gpx7 and the role of.6 in the thyroid papillary carcinoma were investigated, and the immunohistochemical evaluation standard was used. Criteria: each case was randomly observed 5 high times of visual field, according to the percentage and intensity of dyed cells. Positive cell percentage score standard: 10% is 0, 11%~25% is 1, 26%~50% is 2, 51%~75% is 3, 75% is 4; the dyeing strength score is 0, light yellow is 1, brown yellow is 2, Brown is 3. The score of positive cell rate and staining intensity score was the final score, 0 was negative (-), 1~4 was weak positive (+), 5~8 was moderately positive (+ +), 9~12 was strong positive (+ + +).7. Statistical method: statistical analysis was carried out by spss20.0 statistical software, and the data were expressed by mean number of standard deviation, and the differences were compared by independent sample t. Test, if the variance is not homogeneous, we use t 'test. Count data using examples (percentage), group comparison using chi square test. Correlation analysis using Pearson correlation analysis.P0.05 for difference is statistically significant. Results: 1, gpx7 on thyroid papillary carcinoma cell proliferation, apoptosis effect study (1) immunohistochemical results: (1) gpx7 expression The positive rate of.Gpx7 expression in PTC group was 100% in the cytoplasm of thyroid gland. The positive rate of gpx7 expression in group a group was 30%, and the expression of gpx7 in group PTC was significantly higher than that in group A (P0.05). (2) the expression of gpx7 was related to the maximum diameter of the tumor (r=0.601, P0.05), and the maximum diameter of the gpx7 high expression group was (2). 1.56 + 0.56cm) was significantly greater than that of gpx7 low expression group (0.56 + 0.13cm) (P0.05). (2) cell experimental results: (1) the results of two human thyroid papillary carcinoma cell lines TPC-1 and k1.qt-pcr showed that the gpx7 gene had high expression abundance in TPC-1 and K1 cells. Compared with K1 cells, the expression of K1 cells was higher, so K1 cells were selected for subsequent experimental studies (2) after the preparation of the gpx7 gene interfering lentivirus vector, the expression of gpx7 was obviously reduced after the gpx7 gene knockout, which indicated that the target had a knockout effect on the exogenous expression of the gpx7 gene and was an effective target. (3) the gpx7 gene interfered with the lentivirus vector infected K1 cells and observed under the common microscope and the fluorescence microscope. It was found that the cell infection efficiency was above 80% and the cell state was normal. The expression of gpx7 gene in K1 cells was inhibited and the knock reduction efficiency reached 81.5% after the shRNA lentivirus infection was confirmed by qPCR. (4) the results of celigo cell count showed G. The number of cell proliferation in px7 gene knockout group was significantly reduced, and the proliferation rate was only (5 + 0.32) times more than that in first days (5 + 0.32). Compared with the control group (8.44 + 0.26), the proliferation rate decreased significantly. (5) flow cytometry showed that the percentage of apoptosis in gpx7 gene knockout group was (24.08 + 0.28)%, compared with the control group (4.33 + 0.15)%, the percentage of apoptosis was obvious (6) caspase3/7 activity detection showed that the caspase3/7 activity of gpx7 gene knockout group was (257.82 + 21.28), and was significantly increased compared with the control group (100 + 5.38). (7) MTT detection found that the od490 value of gpx7 gene subtraction group increased for fifth days (3.081 + 0.160) times than that of first days (3.081 + 0.160 times), compared with the control group (increased 4.897 + 0.091 times), gpx7 gene. The cell growth multiple of the knockout group decreased significantly. (8) the cell clone formation test showed that the number of gpx7 gene knockout group clones (283 + 6) compared with the control group (710 + 10), significantly reduced.2, the possible mechanism of gpx7 in thyroid papillary carcinoma (1) immunohistochemical results (1) nf- kappa bp65 expressed in the cytoplasm of thyroid cells The expression of.Ptc in group.Ptc was significantly higher than that in group.Ptc group, and the positive expression rate of nf- kappa bp65 was 83.3%. (2) the expression of CyclinD1 expressed in group.Ptc of thyroid nucleus was significantly higher than that in group.Ptc group, and the positive rate of CyclinD1 was 96.7%, and (3) gpx7, nf- kappa bp65, and the expression of cyclinD1 protein showed significant. Positive correlation (r value was 0.721,0.589,0.703, P value was 0.05 respectively). (4) the positive rate of joint detection of gpx7 and nf- kappa bp65 in group PTC was 83.3%, the positive rate of joint detection with CyclinD1 was 100%, and the positive rate of the three joint detection was 83.3%. (2) cell experiment (1) the cell efficiency of the lentivirus infection order was higher, qPCR confirmed that gpx7 gene was effectively knocked down. (2) Wester Nblot results showed that the expression of nf- kappa bp65 protein was not significantly changed after knockout of the gpx7 gene of thyroid papillary carcinoma cell (K1 cell line), and the expression of cyclinD1 protein was increased. The difference was statistically significant (P0.05).3, and the effect of the inflammatory microenvironment on the expression of gpx7 in PTC (1) immunohistochemical results showed that it was accompanied by Hashimoto. The gpx7 protein expression score of thyroid papillary carcinoma (6.21 + 2.29) was lower than that of thyroid papillary carcinoma (8.52 + 2.41). The difference was statistically significant (P0.05). (2) single factor analysis found that the factors affecting the expression of gpx7 were associated with HT, tg-ab, TPO-Ab, tumor location and membrane invasion, among which gpx7 was associated with HT, tg-ab and TPO-Ab levels Negative correlation and positive correlation with tumor location and membrane invasion. (3) multiple factor linear regression analysis found that the factors affecting gpx7 expression were combined ht. (4) clinicopathological features, and that PTC tumors with HT inflammatory environment were mostly limited to unilateral and low incidence of membrane invasion. Conclusion: 1, immunohistochemical and cell experimental results showed GPX7 The high expression of.2 in thyroid papillary carcinoma shows that GPX7 has the role of promoting the proliferation of thyroid papillary carcinoma cells and reducing apoptosis,.3, GPX7, NF- kappa B p65, and the expression of Cyclin D1 protein in thyroid papillary carcinoma is positively correlated, suggesting the occurrence of three cases of thyroid papillary carcinoma and the possible development of thyroid papillary carcinoma. There was no change in the expression of NF- kappa B p65 protein after.4 knockdown, suggesting that the role of GPX7 in papillary thyroid carcinoma is related to NF- NF- B signaling pathway, GPX7

【学位授予单位】：大连医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R736.1

【相似文献】