MiR-145-5p arrests the cell cycle by modulating SMAD5/cyclin D1 to inhibit gastric cancer progression
PurposeThis study aimed to explore the dysregulation of miR-145-5p in gastric cancer (GC) and its effects on the proliferation and cell cycle of GC cells, exploring the potential regulatory mechanism of miR-145-5p in GC.MethodsIn this study, the TCGA database combined with Microarray was used to det...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1619359/full |
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| author | Li Wang Li Wang Jianghong Guo Caixia Lv Luke Kong Luke Kong Jing Cui Zhongshuai Wang Yuanyuan Guo Ruirui Jia Tao Guan Tao Guan Baofeng Yu Feng Li |
| author_facet | Li Wang Li Wang Jianghong Guo Caixia Lv Luke Kong Luke Kong Jing Cui Zhongshuai Wang Yuanyuan Guo Ruirui Jia Tao Guan Tao Guan Baofeng Yu Feng Li |
| author_sort | Li Wang |
| collection | DOAJ |
| description | PurposeThis study aimed to explore the dysregulation of miR-145-5p in gastric cancer (GC) and its effects on the proliferation and cell cycle of GC cells, exploring the potential regulatory mechanism of miR-145-5p in GC.MethodsIn this study, the TCGA database combined with Microarray was used to detect differentially expressed microRNA (miRNA) in GC tissues and cells. Quantitative real-time (qRT)-PCR was used to further verify the expression of miR-145-5p in GC cells and the 41 pairs of GC tissues and adjacent tissues. A retrospective analysis was conducted on the correlation between miR-145-5p and the clinicopathological characteristics of patients with GC. The proliferation ability and cell cycle of AGS and MKN28 were detected by CCK-8, Edu and flow cytometry. The downstream target genes of miR-145-5p were screened by bioinformatics and further verified by the dual-luciferase reporter assay. Immunohistochemistry was used to detect the expression of SMAD5 in GC tissues. Western blot was used to detect cell cycle-related proteins that were regulated by siRNA SMAD5.ResultsThe expression of miR-145-5p was lower in GC tissues and cells compared with adjacent tissues and GES-1, and was related to the poor prognosis of patients with GC. Overexpression of miR-145-5p inhibited the proliferation of GC cells and blocked the cell cycle from G1 phase to S phase. MiR-145-5p targeted SMAD5 to inhibit the proliferation, and arrested the G1/S phase transition of GC cells. Mechanistically, SMAD5 siRNA significantly reduced CCND1 protein expression, Bioinformatics databases predicted that cyclin D1 was the transcription target gene of SMAD5. Moreover, the re-expression of cyclin D1 partially reversed the cell cycle arrest that was induced by SMAD5 depletion in GC cells.ConclusionTaken together, these findings reveal a novel role of the miR-145-5p/SMAD5/cyclin D1 axis in modulating cell cycle progression and cell proliferation in GC, which may provide a prognostic biomarker for GC treatment. |
| format | Article |
| id | doaj-art-2656341eefe9423fbf2cc52f6fc31706 |
| institution | DOAJ |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-2656341eefe9423fbf2cc52f6fc317062025-08-20T02:55:27ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-08-011310.3389/fcell.2025.16193591619359MiR-145-5p arrests the cell cycle by modulating SMAD5/cyclin D1 to inhibit gastric cancer progressionLi Wang0Li Wang1Jianghong Guo2Caixia Lv3Luke Kong4Luke Kong5Jing Cui6Zhongshuai Wang7Yuanyuan Guo8Ruirui Jia9Tao Guan10Tao Guan11Baofeng Yu12Feng Li13Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Effects and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, MOE Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, ChinaDepartment of Central Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Gastroenterology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, ChinaBasic Medical College, Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Medical Laboratory, Jincheng People’s Hospital, Jincheng, ChinaDepartment of Cell Biology, The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaDepartment of Central Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Central Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaRenal Department Blood Purification Center, Shanxi Provincial People’s Hospital, Taiyuan, ChinaDepartment of Hematology, Shanxi Hospital Affiliated to Cancer Hospital/Shanxi Province Cancer Hospital, Cancer Hospital Affiliated to Shanxi Medical University/Chinese Academy of Medical Sciences, Taiyuan, Shanxi, China0Shanxi Provincial Key Laboratory of Lymphoma Precision Diagnosis and Treatment Research, Taiyuan, Shanxi, ChinaDepartment of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Effects and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, MOE Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, ChinaDepartment of Central Laboratory, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaPurposeThis study aimed to explore the dysregulation of miR-145-5p in gastric cancer (GC) and its effects on the proliferation and cell cycle of GC cells, exploring the potential regulatory mechanism of miR-145-5p in GC.MethodsIn this study, the TCGA database combined with Microarray was used to detect differentially expressed microRNA (miRNA) in GC tissues and cells. Quantitative real-time (qRT)-PCR was used to further verify the expression of miR-145-5p in GC cells and the 41 pairs of GC tissues and adjacent tissues. A retrospective analysis was conducted on the correlation between miR-145-5p and the clinicopathological characteristics of patients with GC. The proliferation ability and cell cycle of AGS and MKN28 were detected by CCK-8, Edu and flow cytometry. The downstream target genes of miR-145-5p were screened by bioinformatics and further verified by the dual-luciferase reporter assay. Immunohistochemistry was used to detect the expression of SMAD5 in GC tissues. Western blot was used to detect cell cycle-related proteins that were regulated by siRNA SMAD5.ResultsThe expression of miR-145-5p was lower in GC tissues and cells compared with adjacent tissues and GES-1, and was related to the poor prognosis of patients with GC. Overexpression of miR-145-5p inhibited the proliferation of GC cells and blocked the cell cycle from G1 phase to S phase. MiR-145-5p targeted SMAD5 to inhibit the proliferation, and arrested the G1/S phase transition of GC cells. Mechanistically, SMAD5 siRNA significantly reduced CCND1 protein expression, Bioinformatics databases predicted that cyclin D1 was the transcription target gene of SMAD5. Moreover, the re-expression of cyclin D1 partially reversed the cell cycle arrest that was induced by SMAD5 depletion in GC cells.ConclusionTaken together, these findings reveal a novel role of the miR-145-5p/SMAD5/cyclin D1 axis in modulating cell cycle progression and cell proliferation in GC, which may provide a prognostic biomarker for GC treatment.https://www.frontiersin.org/articles/10.3389/fcell.2025.1619359/fullmiR-145-5pSmad5gastric cancercyclin D1cell cycle |
| spellingShingle | Li Wang Li Wang Jianghong Guo Caixia Lv Luke Kong Luke Kong Jing Cui Zhongshuai Wang Yuanyuan Guo Ruirui Jia Tao Guan Tao Guan Baofeng Yu Feng Li MiR-145-5p arrests the cell cycle by modulating SMAD5/cyclin D1 to inhibit gastric cancer progression Frontiers in Cell and Developmental Biology miR-145-5p Smad5 gastric cancer cyclin D1 cell cycle |
| title | MiR-145-5p arrests the cell cycle by modulating SMAD5/cyclin D1 to inhibit gastric cancer progression |
| title_full | MiR-145-5p arrests the cell cycle by modulating SMAD5/cyclin D1 to inhibit gastric cancer progression |
| title_fullStr | MiR-145-5p arrests the cell cycle by modulating SMAD5/cyclin D1 to inhibit gastric cancer progression |
| title_full_unstemmed | MiR-145-5p arrests the cell cycle by modulating SMAD5/cyclin D1 to inhibit gastric cancer progression |
| title_short | MiR-145-5p arrests the cell cycle by modulating SMAD5/cyclin D1 to inhibit gastric cancer progression |
| title_sort | mir 145 5p arrests the cell cycle by modulating smad5 cyclin d1 to inhibit gastric cancer progression |
| topic | miR-145-5p Smad5 gastric cancer cyclin D1 cell cycle |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1619359/full |
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