FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region
Background: Forkhead box M1 (FOXM1) functions as a transcription factor and is consistently overexpressed in various cancers, including non-small-cell lung-, breast-, cervical-, and colorectal cancer. Its overexpression is associated with poor prognosis in patients with non-small-cell lung cancer, a...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024031785 |
| _version_ | 1827316402043748352 |
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| author | Mengcha Tian Jiaming Li Huihui Wu Yuying Wu |
| author_facet | Mengcha Tian Jiaming Li Huihui Wu Yuying Wu |
| author_sort | Mengcha Tian |
| collection | DOAJ |
| description | Background: Forkhead box M1 (FOXM1) functions as a transcription factor and is consistently overexpressed in various cancers, including non-small-cell lung-, breast-, cervical-, and colorectal cancer. Its overexpression is associated with poor prognosis in patients with non-small-cell lung cancer, although the detailed mechanisms by which FOXM1 promotes the development of non-small-cell lung cancer remain unclear. Objective: The mechanism of FOXM1 in migration, invasion, apoptosis, and viability of lung cancer cells was investigated. Methods: Transwell assay, scratch test, and flow cytometry were employed to study the effects of FOXM1 on migration, invasion, and apoptosis in A549 cells. A quantitative polymerase chain reaction was used to determine the impact of FOXM1 on miR-509-5p expression in A549 cells. Dual-luciferase reporter gene assay and chromatin immunoprecipitation were adopted to investigate the molecular mechanisms of FOXM1 on miR-509-5p expression. Results: FDI-6 (a FOXM1 inhibitor) reduced the protein abundance of FOXM1, thereby increasing the expression of miR-509-5p in A549 cells. Moreover, FDI-6 treatment significantly reduced migration, invasion, and viability of A549 cells while promoting cell apoptosis. Furthermore, miR-509-5p inhibitor obviously alleviated the biological effects of FDI-6 on A549 cells, suggesting that FOXM1 primarily exerted its cancer promoting effect by regulating miR-509-5p. Mechanistically, FOXM1 directly bound to the miR-509-5p promoter to inhibit miR-509-5p expression. Conclusion: FOXM1 directly binds to the promoter region of miR-509-5p to form a negative feedback loop, thereby inhibiting miR-509-5p expression and promoting the development of non-small-cell lung cancer. This study is expected to complement research on the pathogenesis of non-small-cell lung cancer and promote the development of novel therapeutic targets for this disease. |
| first_indexed | 2024-04-24T23:15:07Z |
| format | Article |
| id | doaj.art-8a3fe81d56b5468492b40e359a8c95de |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T23:15:07Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8a3fe81d56b5468492b40e359a8c95de2024-03-17T07:57:29ZengElsevierHeliyon2405-84402024-03-01105e27147FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter regionMengcha Tian0Jiaming Li1Huihui Wu2Yuying Wu3Department of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, ChinaDepartment of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, ChinaDepartment of Clinical Laboratory, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, ChinaDepartment of General Medicine, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, 362000, China; Corresponding author.Background: Forkhead box M1 (FOXM1) functions as a transcription factor and is consistently overexpressed in various cancers, including non-small-cell lung-, breast-, cervical-, and colorectal cancer. Its overexpression is associated with poor prognosis in patients with non-small-cell lung cancer, although the detailed mechanisms by which FOXM1 promotes the development of non-small-cell lung cancer remain unclear. Objective: The mechanism of FOXM1 in migration, invasion, apoptosis, and viability of lung cancer cells was investigated. Methods: Transwell assay, scratch test, and flow cytometry were employed to study the effects of FOXM1 on migration, invasion, and apoptosis in A549 cells. A quantitative polymerase chain reaction was used to determine the impact of FOXM1 on miR-509-5p expression in A549 cells. Dual-luciferase reporter gene assay and chromatin immunoprecipitation were adopted to investigate the molecular mechanisms of FOXM1 on miR-509-5p expression. Results: FDI-6 (a FOXM1 inhibitor) reduced the protein abundance of FOXM1, thereby increasing the expression of miR-509-5p in A549 cells. Moreover, FDI-6 treatment significantly reduced migration, invasion, and viability of A549 cells while promoting cell apoptosis. Furthermore, miR-509-5p inhibitor obviously alleviated the biological effects of FDI-6 on A549 cells, suggesting that FOXM1 primarily exerted its cancer promoting effect by regulating miR-509-5p. Mechanistically, FOXM1 directly bound to the miR-509-5p promoter to inhibit miR-509-5p expression. Conclusion: FOXM1 directly binds to the promoter region of miR-509-5p to form a negative feedback loop, thereby inhibiting miR-509-5p expression and promoting the development of non-small-cell lung cancer. This study is expected to complement research on the pathogenesis of non-small-cell lung cancer and promote the development of novel therapeutic targets for this disease.http://www.sciencedirect.com/science/article/pii/S2405844024031785Non-small cell carcinomaFOXM1miR-509-5pPromoterInhibitors |
| spellingShingle | Mengcha Tian Jiaming Li Huihui Wu Yuying Wu FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region Heliyon Non-small cell carcinoma FOXM1 miR-509-5p Promoter Inhibitors |
| title | FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region |
| title_full | FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region |
| title_fullStr | FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region |
| title_full_unstemmed | FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region |
| title_short | FOXM1 promotes the progression of non-small cell lung cancer by inhibiting miR-509-5p expression via binding to the miR-509-5p promoter region |
| title_sort | foxm1 promotes the progression of non small cell lung cancer by inhibiting mir 509 5p expression via binding to the mir 509 5p promoter region |
| topic | Non-small cell carcinoma FOXM1 miR-509-5p Promoter Inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024031785 |
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