研究硫酸酯酶1在非小细胞肺癌中的抗癌潜力及其潜在机制。
Investigating the anti-cancer potential of sulfatase 1 and its underlying mechanism in non-small cell lung cancer.
作者信息
Zhang Bingling, Luo Daping, Xiang Lan, Chen Jun, Fang Ting
机构信息
Department of Disease Control and Prevention, Zhangqiao Branch, Ningbo Ninth Hospital Medical Health Group, Ningbo, China.
Department of Prevention and Healthcare, Hongtang Branch, Ningbo Ninth Hospital Medical Health Group, Ningbo, China.
出版信息
Cytojournal. 2024 Nov 23;21:52. doi: 10.25259/Cytojournal_71_2024. eCollection 2024.
OBJECTIVE
Patients with non-small cell lung cancer (NSCLC) have poor prognoses. Sulfatase 1 (SULF1) is an extracellular neutral sulfatase and is involved in multiple physiological processes. Hence, this study investigated the function and possible mechanisms of SULF1 in NSCLC.
MATERIAL AND METHODS
Difference in SULF1 expression level between tumors and normal lung tissues was analyzed through bioinformatics and clinical sampling, and the effects of SULF1 expression on prognosis were investigated through Kaplan-Meier analysis. SULF1 level in NSCLC cells was modulated through small interfering ribonucleic acid interference. NSC228155, which is an epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling pathway agonist, was for handling NSCLC cells. SULF1 expression level was tested through quantitative reverse transcriptase real-time polymerase chain reaction. Cell proliferation, migration, and invasion were evaluated with cell counting kit-8, 5-ethynyl-2-deoxyuridine, and transwell assays, and the levels of epithelial-to-mesenchymal transition (EMT)- and EGFR/MAPK pathway-related proteins were detected through Western blot.
RESULTS
Bioinformatics and clinical samples showed that NSCLC tumor tissues had elevated SULF1 expression levels relative to those of normal tissues ( < 0.05). Patients with NSCLC and high SULF1 expression levels experienced poorer prognosis than those of low SULF1 expression levels ( < 0.05). SULF1 knockdown repressed the malignant biological behavior, including proliferation, migration, and invasion, of the NSCLC cells ( < 0.05). Mechanistically, SULF1 knockdown augmented E-cadherin level and abated N-cadherin and vimentin protein levels ( < 0.05). These results confirmed that EMT was inhibited. In addition, the knockdown of SULF1 reduced the phosphorylation of EGFR, extracellular signal-regulated kinase, p38 MAPK and c-Jun N-terminal kinase, and NSC228155 partially reversed these changes, which were affected by SULF1 knockdown. Meanwhile, NSC228155 partially reversed the inhibition of EMT, migration, and invasion affected by SULF1 knockdown.
CONCLUSION
SULF1 knockdown inhibits the proliferation, migration, invasion, and EMT of NSCLC cells by inactivating EGFR/MAPK pathway.
目的
非小细胞肺癌（NSCLC）患者预后较差。硫酸酯酶1（SULF1）是一种细胞外中性硫酸酯酶，参与多种生理过程。因此，本研究探讨SULF1在NSCLC中的功能及可能机制。
材料与方法
通过生物信息学和临床采样分析肿瘤组织与正常肺组织中SULF1表达水平的差异，并通过Kaplan-Meier分析研究SULF1表达对预后的影响。通过小干扰核糖核酸干扰调节NSCLC细胞中的SULF1水平。使用表皮生长因子受体（EGFR）/丝裂原活化蛋白激酶（MAPK）信号通路激动剂NSC228155处理NSCLC细胞。通过定量逆转录实时聚合酶链反应检测SULF1表达水平。使用细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷和Transwell实验评估细胞增殖、迁移和侵袭能力，并通过蛋白质免疫印迹法检测上皮-间质转化（EMT）和EGFR/MAPK通路相关蛋白的水平。
结果
生物信息学和临床样本显示，NSCLC肿瘤组织中SULF1表达水平相对于正常组织升高（<0.05）。SULF1表达水平高的NSCLC患者预后比SULF1表达水平低的患者差（<0.05）。敲低SULF1可抑制NSCLC细胞的恶性生物学行为，包括增殖、迁移和侵袭（<0.05）。机制上，敲低SULF1可增加E-钙黏蛋白水平，降低N-钙黏蛋白和波形蛋白的蛋白水平（<0.05）。这些结果证实EMT受到抑制。此外，敲低SULF1可降低EGFR、细胞外信号调节激酶、p38 MAPK和c-Jun氨基末端激酶的磷酸化水平，NSC228155可部分逆转这些受SULF1敲低影响的变化。同时，NSC228155可部分逆转敲低SULF1对EMT、迁移和侵袭的抑制作用。
结论
敲低SULF1可通过使EGFR/MAPK通路失活来抑制NSCLC细胞的增殖、迁移、侵袭和EMT。
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