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右美托咪定增加分泌型SERPINE1表达对甲状腺癌细胞恶性生物学行为的影响
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| 篇名： | 右美托咪定增加分泌型SERPINE1表达对甲状腺癌细胞恶性生物学行为的影响 |
| TITLE： | Effects of increased secretory SERPINE1 expression by dexmedetomidine on the malignant biological behavior of thyroid carcinoma cells |
| 摘要： | 目的 探讨右美托咪定（DEX）增加分泌型丝氨酸蛋白酶抑制剂家族E成员1（SERPINE1）蛋白表达对甲状腺癌（THCA）细胞恶性生物学行为的影响。方法使用1、10、100nmol/L的DEX处理THCA细胞（KTC-1、TPC-1），检测其活力、克隆形成率、迁移率和侵袭数。通过全基因组测序和基因本体等富集分析探讨DEX在THCA中的潜在生物学功能；通过蛋白质-蛋白质相互作用网络挖掘DEX的核心靶点，并评估DEX核心靶点的表达特征及其与患者预后的关系。检测DEX对2种THCA细胞中核心靶点mRNA、蛋白表达及蛋白分泌的影响，通过敲减核心靶点来初步验证该靶点对DEX相关作用的影响。结果与对照（0nmol/LDEX）组比较，1、10、100nmol/LDEX组2种THCA细胞的活力（1nmol/LDEX组KTC-1细胞24h时除外）均显著升高，克隆形成率、迁移率（1nmol/LDEX组2种THCA细胞除外）和侵袭数亦显著升高且呈浓度依赖性（P＜0.05）。DEX处理或不处理的2种THCA细胞中，共有287个差异表达基因（75个上调、212个下调），富集于磷脂酰肌醇3激酶/蛋白激酶B、Wnt和衰老相关分泌表型等信号通路；SERPINE1是DEX促THCA的核心靶点，其mRNA及蛋白在THCA组织/细胞中的表达均显著升高，且与患者的不良预后有关（P＜0.05）；与对照组比较，1、10、100nmol/LDEX组2种THCA细胞中SERPINE1mRNA及蛋白的表达均显著上调，且在条件培养基中该蛋白的分泌亦显著增多，均呈浓度依赖性（P＜0.05）。敲减SERPINE1后，DEX对2种THCA细胞增殖、克隆形成、迁移、侵袭能力的促进作用受到了显著抑制（P＜0.05）。结论DEX能够促进THCA细胞的增殖、迁移和侵袭，上述作用可能与增加分泌型SERPINE1蛋白的表达有关。 |
| ABSTRACT： | OBJECTIVE To explore the effects of dexmedetomidine （DEX） increasing serpin peptidase inhibitor clade E member 1 （SERPINE1） protein on the malignant biological behavior of thyroid carcinoma （THCA） cells. METHODS THCA cells （KTC-1， TPC-1） were treated with 1， 10 and 100 nmol/L DEX， and their viabilities， clone formation rates， migration rates and invasion number were examined. Potential biological functions of DEX in THCA cells were analyzed through whole genome sequencing and gene ontology enrichment analysis. The core targets of DEX were mined through a protein-protein interaction network. The expression characteristics of DEX core targets and their relationship with patient prognosis were evaluated. The effects of DEX on mRNA and protein expressions of core targets and protein secretion in 2 types of THCA cells were detected， and the effects of this target on DEX-related effects were validated preliminarily by knocking down the core target. RESULTS Compared with the control group （0 nmol/L DEX）， DEX at 1， 10 and 100 nmol/L significantly increased the viabilities of 2 types of THCA cells （except for the KTC-1 cells in the 1 nmol/L DEX group at 24 h）， concentration-dependently elevated the rates of clone formation， migration rates （except for 2 types of THCA cells in 1 nmol/L DEX group）， and the number of invasion （P＜0.05）. A total of 287 differently expressed genes （75 up- tongxueyan180@163.com regulated and 212 down-regulated） were enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B， Wnt， and senescence-associated secretory phenotypes in the 2 kinds of DEX-treated or non-treated THCA cells. SERPINE1 was a core target of DEX for THCA， and its mRNA and protein expression in THCA tissues/cells were significantly elevated and associated with poor prognosis of the patients （P＜0.05）. Compared with the control group， mRNA and protein expression of SERPINE1 was significantly up-regulated in 2 types of cells in the 1， 10 and 100 nmol/L DEX groups， while the secretion of this protein in conditioned medium was also significantly increased， all of which showed concentration-dependence （P＜0.05）. After knocking down SERPINE1， the promoting effects of DEX on the proliferation， colony formation， migration and invasion abilities of two types of THCA cells were significantly inhibited （P＜0.05）. CONCLUSIONS DEX can promote the proliferation， migration and invasion of THCA cell， and the above effects may be associated with the expression of increased secretory SERPINE1 protein. |
| 期刊： | 2025年第36卷第10期 |
| 作者： | 童雪燕；蒋文锋；曾亮平；林燕 |
| AUTHORS： | TONG Xueyan，JIANG Wenfeng，ZENG Liangping，LIN Yan |
| 关键字： | 右美托咪定；甲状腺癌；SERPINE1；恶性生物学行为 |
| KEYWORDS： | dexmedetomidine； thyroid carcinoma； SERPINE1； malignant biological behavior |
| 阅读数： | 3 次 |
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