Introduction: Non-small cell lung cancer (NSCLC) is a type of malignant tumor with high morbidity as well as mortality. The process of lung cancer may be driven by cancer stem cells. It was known that MFAP5 enhanced the occurrence of diverse types of cancer. Also, MFAP5 has the potential to induce the degradation of FBW7 which is a tumor suppressor. Lower levels of FBW7 enhance the stability of Sox9, which is the cancer stem cell-related protein. However, whether the MFAP5 can modulate the stem cell features of NSCLC cells by modulating the FBW7/Sox9 axis is unclear. Therefore, this study aimed to explore the role of MFAP5/FBW7/Sox9 axis on the stem cell features of NSCLC cells and develop a new treatment of this carcinoma. Material and Methods: In this study, we explored the effects of MFAP5 on the stem cell features of NSCLC cells for the first time. We established MFAP5 overexpression and knockdown NSCLC cells. Clone formation assays and cell sphere culture assays were conducted for the exploration of the growth and stem cell features of these cells. Western blotting was applied for the detection of Sox9 and FBW7 expression in these cells. CHX was applied for the treatment of these cells for the detection of degradation of Sox9. Finally, we overexpressed the Sox9 in MFAP5 knockdown NSCLC cells. Results: MFAP5 promoted the growth and stem cell features of these cells. Knockdown of MFAP5 induced higher levels of FBW7 while restricting the expression of Sox9. Knockdown of MFAP5 aggravated the degradation of Sox9. Overexpression of Sox9 abrogated the efficacy of MFAP5 inhibition on the growth as well as stem cell features of these cells. The results of this study clarified the role of MFAP5/FBW7/Sox9 axis on the development of non-small cell lung cancer cells, providing the potential therapeutic target for the clinical treatment of NSCLC. Conclusion: MFAP5 maintained the stem cell features of non-small cell lung cancer cells by modulating FBW7/Sox9 axis.

中文翻译：

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MFAP5通过调节FBW/Sox9轴增强非小细胞肺癌细胞的干细胞特征

简介：非小细胞肺癌（NSCLC）是一种发病率和死亡率较高的恶性肿瘤。肺癌的发生过程可能是由癌症干细胞驱动的。众所周知，MFAP5 会增加多种癌症的发生。此外，MFAP5 有可能诱导肿瘤抑制因子 FBW7 的降解。较低水平的 FBW7 增强了 Sox9（癌症干细胞相关蛋白）的稳定性。然而，MFA​​P5是否可以通过调节FBW7/Sox9轴来调节NSCLC细胞的干细胞特征尚不清楚。因此，本研究旨在探讨MFAP5/FBW7/Sox9轴对NSCLC细胞干细胞特征的作用，并开发该癌症的新治疗方法。材料和方法：在本研究中，我们首次探讨了 MFAP5 对 NSCLC 细胞干细胞特征的影响。我们建立了 MFAP5 过表达和敲低 NSCLC 细胞。进行克隆形成测定和细胞球培养测定以探索这些细胞的生长和干细胞特征。应用Western blotting检测这些细胞中Sox9和FBW7的表达。应用 CHX 处理这些细胞以检测 Sox9 的降解。最后，我们在 MFAP5 敲低的 NSCLC 细胞中过表达 Sox9。结果：MFAP5 促进这些细胞的生长和干细胞特征。MFAP5 的敲低诱导了更高水平的 FBW7，同时限制了 Sox9 的表达。MFAP5 的敲低加剧了 Sox9 的降解。Sox9 的过度表达消除了 MFAP5 抑制对这些细胞的生长以及干细胞特征的功效。该研究结果阐明了MFAP5/FBW7/Sox9轴在非小细胞肺癌细胞发生发展中的作用，为NSCLC的临床治疗提供了潜在的治疗靶点。结论：MFAP5通过调节FBW7/Sox9轴维持非小细胞肺癌细胞的干细胞特征。