DNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progression
Abstract Background The dysregulation of SOXs is related to tumor invasion, metastasis, proliferation, apoptosis, and epithelial-mesenchymal transition. This research sought to investigate the function and mechanisms of SOX21 in gastric cancer (GC). Methods Multiple databases were included to determ...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-025-14577-z |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849764391240597504 |
|---|---|
| author | Jie Wei Song Xue Xinglong Du Yuanfei Dai Yuting Ji Guangsi He |
| author_facet | Jie Wei Song Xue Xinglong Du Yuanfei Dai Yuting Ji Guangsi He |
| author_sort | Jie Wei |
| collection | DOAJ |
| description | Abstract Background The dysregulation of SOXs is related to tumor invasion, metastasis, proliferation, apoptosis, and epithelial-mesenchymal transition. This research sought to investigate the function and mechanisms of SOX21 in gastric cancer (GC). Methods Multiple databases were included to determine the hub transcription factors in GC. In addition, RT-qPCR and Western blot were used to validate gene expression in tissues from GC patients. CCK-8, EdU, colony formation, wound healing, Transwell assays, and a xenograft tumor model were used to determine the function of SOX21 in GC. The targets of SOX21 were predicted and verified using ChIP, dual-luciferase reporter, and functional assays. SOX21 DNA methylation in GC cells was determined by qMSP. Rescue experiments were carried out in GC cells with DNMT1 silencing alone or in combination with SOX21 silencing. Results SOX21 was downregulated in GC tissues and cells. Ectopic expression of SOX21 inhibited cell growth, invasion, and migration, and induced apoptosis of GC cells. CKS2 was a target of SOX21, and overexpression of CKS2 promoted cell viability and mobility in GC cells overexpressing SOX21. The downregulation of SOX21 was related to the DNA hypermethylation catalyzed by DNMT1. The silencing of SOX21, by contrast, overturned the anti-tumor effects of sh-DNMT1 in vitro and in vivo. Conclusion Our data showed that DNMT1 overexpression upregulated CKS2 expression via hypermethylation of SOX21, thus promoting GC cell proliferation and growth, indicating that the DNMT1/SOX21/CKS2 axis could be a target for GC treatment. |
| format | Article |
| id | doaj-art-e081be659e98403783a3f9b05da2ba21 |
| institution | DOAJ |
| issn | 1471-2407 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj-art-e081be659e98403783a3f9b05da2ba212025-08-20T03:05:09ZengBMCBMC Cancer1471-24072025-07-0125111810.1186/s12885-025-14577-zDNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progressionJie Wei0Song Xue1Xinglong Du2Yuanfei Dai3Yuting Ji4Guangsi He5Department of Oncology, The Affiliated Chuzhou Hospital of Anhui Medical University (The First People’s Hospital of Chuzhou)Department of Oncology, The Affiliated Chuzhou Hospital of Anhui Medical University (The First People’s Hospital of Chuzhou)Department of Oncology, The Affiliated Chuzhou Hospital of Anhui Medical University (The First People’s Hospital of Chuzhou)Department of Oncology, The Affiliated Chuzhou Hospital of Anhui Medical University (The First People’s Hospital of Chuzhou)Department of Oncology, The Affiliated Chuzhou Hospital of Anhui Medical University (The First People’s Hospital of Chuzhou)Department of Oncology, The Affiliated Chuzhou Hospital of Anhui Medical University (The First People’s Hospital of Chuzhou)Abstract Background The dysregulation of SOXs is related to tumor invasion, metastasis, proliferation, apoptosis, and epithelial-mesenchymal transition. This research sought to investigate the function and mechanisms of SOX21 in gastric cancer (GC). Methods Multiple databases were included to determine the hub transcription factors in GC. In addition, RT-qPCR and Western blot were used to validate gene expression in tissues from GC patients. CCK-8, EdU, colony formation, wound healing, Transwell assays, and a xenograft tumor model were used to determine the function of SOX21 in GC. The targets of SOX21 were predicted and verified using ChIP, dual-luciferase reporter, and functional assays. SOX21 DNA methylation in GC cells was determined by qMSP. Rescue experiments were carried out in GC cells with DNMT1 silencing alone or in combination with SOX21 silencing. Results SOX21 was downregulated in GC tissues and cells. Ectopic expression of SOX21 inhibited cell growth, invasion, and migration, and induced apoptosis of GC cells. CKS2 was a target of SOX21, and overexpression of CKS2 promoted cell viability and mobility in GC cells overexpressing SOX21. The downregulation of SOX21 was related to the DNA hypermethylation catalyzed by DNMT1. The silencing of SOX21, by contrast, overturned the anti-tumor effects of sh-DNMT1 in vitro and in vivo. Conclusion Our data showed that DNMT1 overexpression upregulated CKS2 expression via hypermethylation of SOX21, thus promoting GC cell proliferation and growth, indicating that the DNMT1/SOX21/CKS2 axis could be a target for GC treatment.https://doi.org/10.1186/s12885-025-14577-zGastric cancerDNMT1SOX21CKS2Hypermethylation |
| spellingShingle | Jie Wei Song Xue Xinglong Du Yuanfei Dai Yuting Ji Guangsi He DNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progression BMC Cancer Gastric cancer DNMT1 SOX21 CKS2 Hypermethylation |
| title | DNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progression |
| title_full | DNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progression |
| title_fullStr | DNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progression |
| title_full_unstemmed | DNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progression |
| title_short | DNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progression |
| title_sort | dnmt1 blocks sox21 repressed cks2 transcription to promote gastric cancer progression |
| topic | Gastric cancer DNMT1 SOX21 CKS2 Hypermethylation |
| url | https://doi.org/10.1186/s12885-025-14577-z |
| work_keys_str_mv | AT jiewei dnmt1blockssox21repressedcks2transcriptiontopromotegastriccancerprogression AT songxue dnmt1blockssox21repressedcks2transcriptiontopromotegastriccancerprogression AT xinglongdu dnmt1blockssox21repressedcks2transcriptiontopromotegastriccancerprogression AT yuanfeidai dnmt1blockssox21repressedcks2transcriptiontopromotegastriccancerprogression AT yutingji dnmt1blockssox21repressedcks2transcriptiontopromotegastriccancerprogression AT guangsihe dnmt1blockssox21repressedcks2transcriptiontopromotegastriccancerprogression |