Targeting of the anti-apoptotic gene survivin in human thyroid carcinoma.
Targeting of the anti-apoptotic gene survivin in human thyroid carcinoma.
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DOI：
10.3892/ijmm.2012.1046
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发表时间：
2012-09
影响因子：
5.4
通讯作者：
Hoang-Vu C
中科院分区：
文献类型：
--
作者：
Chen Z;Liu N;Zhu G;Dralle H;Hoang-Vu C
Survivin是一种新型的凋亡抑制因子。它的基因与杆状病毒基因有关，杆状病毒基因被认为在胎儿发育和癌症中起着至关重要的作用。我们试图确定生存素在甲状腺肿和癌组织中的表达，并评估其在人类甲状腺疾病的预后价值。在本研究中，我们应用小干扰RNA（siRNA）针对生存素，以确定降低高组成性水平的这种蛋白在FTC-133甲状腺滤泡癌细胞系的影响。应用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法，对90例原发性甲状腺癌和良性甲状腺肿（乳头状癌33例，滤泡状癌24例，未分化癌18例，甲状腺肿15例）术后标本中Survivin的表达与相关临床病理资料进行比较。对于人滤泡性甲状腺癌细胞系中的siRNA处理，使用荧光素标记的双链超纯siRNA。RT-PCR在75例甲状腺肿瘤和15例良性甲状腺肿中分别检测到67例（89.3%）和4例（4.0%）Survivin基因的表达。免疫组化显示65/75（86.7%）例甲状腺癌组织呈阳性表达，而15例良性甲状腺肿组织均无表达。甲状腺癌组织中Survivin mRNA和蛋白表达水平均显著高于良性甲状腺肿组织（P<0.001）。Survivin在pT 3/pT 4及有淋巴结转移的肿瘤组织中的表达明显增高（P<0.05）。与无远处转移的肿瘤相比，有远处转移的肿瘤表现出更高的生存素表达。Survivin在未分化癌中的表达高于分化癌。Survivin的表达与患者年龄、性别、组织学分型及病理分期无明显相关性。我们的进一步研究表明，针对生存素的siRNA显著降低了生存素的蛋白表达。总之，我们得出结论，生存素表达表明甲状腺癌细胞在体内更具侵袭性和转移能力。Survivin可作为甲状腺癌诊断和治疗的标志物，并可作为甲状腺癌治疗策略的重要靶点。我们的siRNA沉默的结果表明，siRNA可能有潜力作为治疗人类甲状腺癌的治疗方式。
Survivin is a novel apoptosis inhibitor. Its gene is related to the baculovirus gene, which is believed to play a crucial role in fetal development and in cancer. We attempted to determine the expression of survivin in both thyroid goiter and carcinoma tissues, and to evaluate its prognostic value in human thyroid disease. In the present study, we applied small interfering RNA (siRNA) directed against survivin to determine the effects of decreasing the high constitutive levels of this protein in the FTC-133 thyroid follicular cancer cell line. Using reverse transcription PCR and immunohistochemistry, we compared the expression of survivin with relevant clinical and pathological data of 90 postsurgical specimens from patients with primary thyroid carcinoma and patients with benign goiter (33 with papillary thyroid cancer, 24 with follicular thyroid cancer, 18 with undifferentiated thyroid cancer and 15 cases with goiter). For the siRNA treatment in a human follicular thyroid carcinoma cell line, fluorescein-labeled double-stranded ultrapure siRNAs were used. RT-PCR identified the survivin transcript in 67/75 (89.3%) tumor samples and in 4/15 benign goiter samples. Immunohistochemical analysis showed positive immunoreactivity in 65/75 (86.7%) carcinomas while no expression was noted in all of the 15 benign goiter tissues. Survivin mRNA and protein levels were significantly higher in cancer tissues compared to benign goiter tissues (P<0.001). Higher survivin expression was found in the tumor tissues of pT3/pT4 and in the tumors with lymph node metastasis (P<0.05). Tumors with distant metastasis demonstrated higher survivin expression compared to the tumors without distant metastasis. Additionally, the expression of survivin in undifferentiated carcinomas was higher than that in differentiated ones. There was no significant correlation between survivin expression and age, gender, histological subtype and pathological stage. Our additional studies demonstrated that siRNA directed against survivin markedly decreased the protein expression of survivin. In conclusion, we conclude that survivin expression indicates more aggressive behavior and metastatic ability in thyroid cancer cells in vivo. Survivin can be used as a diagnostic and therapeutic marker for thyroid carcinoma and an important target in the strategy of thyroid cancer therapy. Our results of siRNA silencing indicate that siRNA may have potential as a therapeutic modality in the treatment of human thyroid cancer.
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