MFAP5 Strengthened the Stem Cell Features of Non-small Cell Lung Cancer Cells by Regulating the FBW/Sox9 Axis.

IF 2.2 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Current pharmaceutical biotechnology Pub Date : 2025-01-01 DOI:10.2174/0113892010259632240213091136

Chun Du, Zijuan Qi, Wei Zhang

{"title":"MFAP5 Strengthened the Stem Cell Features of Non-small Cell Lung Cancer Cells by Regulating the FBW/Sox9 Axis.","authors":"Chun Du, Zijuan Qi, Wei Zhang","doi":"10.2174/0113892010259632240213091136","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":10881,"journal":{"name":"Current pharmaceutical biotechnology","volume":" ","pages":"235-245"},"PeriodicalIF":2.2000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current pharmaceutical biotechnology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113892010259632240213091136","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

MFAP5通过调控FBW/Sox9轴加强非小细胞肺癌细胞的干细胞特征

导言非小细胞肺癌（NSCLC）是一种发病率和死亡率都很高的恶性肿瘤。肺癌的发生过程可能是由癌症干细胞驱动的。众所周知，MFAP5 可促进多种癌症的发生。此外，MFAP5 有可能诱导肿瘤抑制因子 FBW7 的降解。较低水平的 FBW7 会增强肿瘤干细胞相关蛋白 Sox9 的稳定性。然而，MFAP5是否能通过调节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，并开发治疗这种癌症的新方法：本研究首次探讨了MFAP5对NSCLC细胞干细胞特征的影响。我们建立了过表达和敲除 MFAP5 的 NSCLC 细胞。我们进行了克隆形成试验和细胞球培养试验，以探索这些细胞的生长和干细胞特征。用 Western 印迹法检测这些细胞中 Sox9 和 FBW7 的表达。用CHX处理这些细胞，以检测Sox9的降解情况。最后，我们在MFAP5基因敲除的NSCLC细胞中过表达了Sox9：结果：MFAP5促进了这些细胞的生长和干细胞特征。结果：MFAP5促进了这些细胞的生长和干细胞特征。敲除MFAP5会诱导更高水平的FBW7，同时限制Sox9的表达。敲除 MFAP5 会加剧 Sox9 的降解。Sox9的过度表达削弱了MFAP5抑制对这些细胞的生长和干细胞特征的影响。该研究结果阐明了MFAP5/FBW7/Sox9轴在非小细胞肺癌细胞发育过程中的作用，为临床治疗NSCLC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。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Current pharmaceutical biotechnology 医学-生化与分子生物学

CiteScore

5.60

自引率

3.60%

发文量

203

审稿时长

6 months

期刊介绍： Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal includes timely in-depth reviews, original research articles and letters written by leaders in the field, covering a range of current topics in scientific areas of Pharmaceutical Biotechnology. Invited and unsolicited review articles are welcome. The journal encourages contributions describing research at the interface of drug discovery and pharmacological applications, involving in vitro investigations and pre-clinical or clinical studies. Scientific areas within the scope of the journal include pharmaceutical chemistry, biochemistry and genetics, molecular and cellular biology, and polymer and materials sciences as they relate to pharmaceutical science and biotechnology. In addition, the journal also considers comprehensive studies and research advances pertaining food chemistry with pharmaceutical implication. Areas of interest include: DNA/protein engineering and processing Synthetic biotechnology Omics (genomics, proteomics, metabolomics and systems biology) Therapeutic biotechnology (gene therapy, peptide inhibitors, enzymes) Drug delivery and targeting Nanobiotechnology Molecular pharmaceutics and molecular pharmacology Analytical biotechnology (biosensing, advanced technology for detection of bioanalytes) Pharmacokinetics and pharmacodynamics Applied Microbiology Bioinformatics (computational biopharmaceutics and modeling) Environmental biotechnology Regenerative medicine (stem cells, tissue engineering and biomaterials) Translational immunology (cell therapies, antibody engineering, xenotransplantation) Industrial bioprocesses for drug production and development Biosafety Biotech ethics Special Issues devoted to crucial topics, providing the latest comprehensive information on cutting-edge areas of research and technological advances, are welcome. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.