Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu, China.
State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214000, Jiangsu, China.
J Cell Sci. 2019 Aug 22;132(16):jcs231399. doi: 10.1242/jcs.231399.
Papillary thyroid cancer (PTC), the most common thyroid malignancy, has a strong propensity for cervical lymph node metastasis (LNM), which increases the risk of locoregional recurrence and decreases survival probability in some high-risk groups. Hence, there is a pressing requirement for a reliable biomarker to predict LNM in thyroid cancer. In the present study, MKL1 (also known as MRTFA) expression was significantly increased in PTC patients with LNM compared with those without. Further receiver operating characteristic (ROC) analysis showed that MKL1 expression had a diagnostic value in the differentiation of LNM in PTC. Furthermore, Kaplan-Meier analysis revealed that high MKL1 expression was associated with significantly decreased survival in PTC. Additionally, our study indicated that MKL1 promoted the migration and invasion of PTC cells. MKL1 interacted with and recruited Smad3 to the promoter of MMP2 to activate MMP2 transcription upon treatment with TGF-β. Moreover, there was significant correlation between expression of TGF-β, MKL1 and MMP2 in our clinical cohort of specimens from individuals with PTC. Our results suggest that the detection of MKL1 expression could be used to predict cervical LNM and inform post-operative follow-up in individuals with PTC.
甲状腺乳头状癌（PTC）是最常见的甲状腺恶性肿瘤，具有很强的颈部淋巴结转移（LNM）倾向，这增加了局部区域复发的风险，并降低了某些高危人群的生存概率。因此，迫切需要一种可靠的生物标志物来预测甲状腺癌的 LNM。在本研究中，MKL1（也称为 MRTFA）在有 LNM 的 PTC 患者中的表达明显高于无 LNM 的患者。进一步的接收者操作特征（ROC）分析表明，MKL1 表达在 PTC 的 LNM 鉴别诊断中有一定的诊断价值。此外，Kaplan-Meier 分析表明，MKL1 高表达与 PTC 患者的生存率显著降低有关。此外，我们的研究表明，MKL1 促进了 PTC 细胞的迁移和侵袭。MKL1 与 Smad3 相互作用，并将 Smad3 募集到 MMP2 的启动子上，在 TGF-β 处理后激活 MMP2 转录。此外，在我们的 PTC 患者临床标本队列中，TGF-β、MKL1 和 MMP2 的表达之间存在显著相关性。我们的研究结果表明，检测 MKL1 表达可用于预测甲状腺癌的颈部 LNM，并为 PTC 患者的术后随访提供信息。
