2022 年第 5 期 第 17 卷

狐猴酪氨酸激酶3基因在甲状腺癌发病及进展中的作用及机制研究

Role and mechanism of lemur tyrosine kinase-3 gene in the pathogenesis and progression of thyroid cancer

作者：路璐1何代玉2王冰2廉静1

英文作者：Lu Lu1 He Daiyu2 Wang Bing2 Lian Jing1

单位：1哈尔滨医科大学附属第四医院放疗科，哈尔滨150001；2黑龙江省大庆龙南医院普外科，大庆163712

英文单位：1Department of Radiotherapy the Fourth Affiliated Hospital of Harbin Medical University Harbin 150001 China; 2Department of General Surgery Daqing Longnan Hospital Heilongjiang Province Daqing 163712 China

关键词：甲状腺癌；狐猴酪氨酸激酶3；增殖；凋亡；侵袭

英文关键词：Thyroidcancer;Lemurtyrosinekinase-3;Proliferation;Apoptosis;Invasion

• 摘要：

• 目的 探寻狐猴酪氨酸激酶3（LMTK3）基因对于甲状腺癌细胞的增殖、侵袭及迁徙和凋亡等方面的影响，寻找甲状腺癌的治疗靶点以及早期诊断的分子标志物。方法 通过检测良恶性甲状腺肿瘤患者及健康志愿者血清中LMTK3含量，确定LMTK3的表达是否有差异。免疫组织化学法检测良恶性甲状腺肿瘤组织及正常甲状腺组织中LMTK3蛋白表达水平的差异。细胞水平转染小干扰RNA后分别通过噻唑蓝、Tunel、Transwell方法检测LMTK3对甲状腺癌细胞的存活率、生长周期、迁移和侵袭力等方面的影响。结果 LMTK3水平在不同临床分期、病理分型的甲状腺癌患者间差异有统计学意义（均P<0.05）。甲状腺癌患者的LMTK3水平显著高于良性甲状腺肿瘤患者和健康志愿者［（0.64±0.27）μg/L比（0.37±0.13）、（0.34±0.09）μg/L］，差异均有统计学意义（均P<0.05）。转染小干扰RNA后甲状腺癌细胞的存活率显著降低，细胞周期G0/G1期占比显著降低、S和G2/M期占比显著升高，细胞凋亡率显著升高，迁移和侵袭能力受明显抑制（均P<0.05）。结论  LMTK3与甲状腺癌有着密切的关系，LMTK3可能成为一个预测甲状腺癌的有价值的生物学标志物。沉默LMTK3基因可抑制甲状腺癌细胞的增殖、侵袭及迁徙，并促进凋亡。LMTK3可能成为甲状腺癌治疗的一个新的靶点。

• Objective  To explore the effects of lemur tyrosine kinase-3(LMTK3) gene on proliferation, invasion, migration and apoptosis of thyroid cancer cells, and to search therapeutic targets and molecular markers for early diagnosis of thyroid cancer. Methods The serum level of LMTK3 was determined in patients with benign and malignant thyroid tumors and healthy volunteers, and the difference of LMTK3 expression was analyzed. Immunohistochemical method was used to detect the difference of LMTK3 protein expression among benign and malignant thyroid tumors and normal thyroid tissues. After small interfering RNA (siRNA) transfected at the cell level, the effects of LMTK3 on the survival rate, growth cycle, migration and invasiveness of thyroid cancer cells were examined by methyl thiazolyl tetrazolium, Tunel and Transwell methods. Results  There were significant differences in the level of LMTK3 among thyroid cancer patients with different clinical stages and pathological types(all P<0.05). The level of LMTK3 in patients with thyroid cancer was significantly higher than that in patients with benign thyroid tumor and healthy volunteers［(0.64±0.27)μg/L vs (0.37±0.13), (0.34±0.09)μg/L］(both P<0.05). After the siRNA transfection, the thyroid cancer cell survival rate was significantly down-regulated, G0/G1 phase rate was significantly down-regulated, while S phase and G2/M phase rates were significantly up-regulated, cell apoptosis rate was significantly up-regulated, and cell migration and invasion were significantly inhibited(all P<0.05). Conclusions LMTK3 is closely related to thyroid cancer. It may be a valuable biomarker for predicting thyroid cancer. Silencing LMTK3 gene inhibits the proliferation, invasion and migration of thyroid cancer cells and promotes apoptosis. LMTK3 may be a new therapeutic targets in patients with thyroid cancer.