Department of Otolaryngology‑Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong 250022, P.R. China.
Int J Mol Med. 2024 Nov;54(5). doi: 10.3892/ijmm.2024.5423. Epub 2024 Sep 20.
The present study aimed to investigate the role and mechanism of inhibin βA (INHBA) in thyroid cancer (TC), and to determine its potential impact on the aggressive behavior of TC cells. The present study employed a comprehensive approach, using public databases, such as the Gene Expression Omnibus and The Cancer Genome Atlas, to identify and analyze the expression of INHBA in TC. Cell transfection, reverse transcription‑quantitative PCR, western blot analysis, immunohistochemistry and assays were conducted to investigate the functional effects of INHBA on TC. In addition, the present study explored the molecular mechanisms underlying the effects of INHBA, focusing on the potential impact on the RhoA signaling pathway and associated molecular cascades. Bioinformatics analysis revealed a significant association between INHBA expression and TC, and INHBA expression was markedly upregulated in TC tissues compared with in healthy control tissues. The results of functional studies demonstrated that INHBA overexpression increased the migration and invasion of TC cells, and the opposite result was observed following INHBA knockdown. Mechanistic investigations indicated that INHBA modulated the RhoA pathway, leading to alterations in the phosphorylation status of LIM kinase 1 (LIMK) and cofilin, key regulators of cytoskeletal dynamics and cell motility. Following the introduction of transfected TC cells into zebrafish and nude mouse models, the results of the present study demonstrated that INHBA knockdown attenuated the metastatic potential of TC cells. In conclusion, INHBA may serve a pivotal role in promoting the aggressive phenotype of TC cells through modulating the RhoA/LIMK/cofilin signaling axis. These findings highlight INHBA as a potential biomarker and therapeutic target for the management of aggressive TC.
本研究旨在探讨抑制素β A (INHBA) 在甲状腺癌 (TC) 中的作用和机制，并确定其对 TC 细胞侵袭性行为的潜在影响。本研究采用综合方法，利用公共数据库，如基因表达综合数据库和癌症基因组图谱，鉴定和分析 INHBA 在 TC 中的表达。通过细胞转染、逆转录-定量 PCR、Western blot 分析、免疫组织化学和测定，研究 INHBA 对 TC 的功能影响。此外，本研究还探讨了 INHBA 作用的分子机制，重点关注其对 RhoA 信号通路及相关分子级联的潜在影响。生物信息学分析显示 INHBA 表达与 TC 之间存在显著关联，与健康对照组织相比，TC 组织中 INHBA 的表达明显上调。功能研究结果表明，INHBA 过表达可增加 TC 细胞的迁移和侵袭，而 INHBA 敲低则观察到相反的结果。机制研究表明，INHBA 调节 RhoA 通路，导致 LIM 激酶 1 (LIMK) 和丝切蛋白的磷酸化状态发生改变，而 LIMK 和丝切蛋白是细胞骨架动力学和细胞迁移的关键调节因子。将转染的 TC 细胞引入斑马鱼和裸鼠模型后，本研究的结果表明，INHBA 敲低可减弱 TC 细胞的转移潜能。综上所述，INHBA 通过调节 RhoA/LIMK/丝切蛋白信号轴，可能在促进 TC 细胞侵袭表型中发挥关键作用。这些发现表明 INHBA 可能是管理侵袭性 TC 的潜在生物标志物和治疗靶点。
