Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMT
Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors of the urinary system. Distant metastasis is the leading cause of poor prognosis in ccRCC. However, ccRCC is found poorly responsitive to radiotherapy and chemotherapy. Effective therapeutic strategies for it...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2022-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-01145-8 |
| _version_ | 1818504965408161792 |
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| author | Ning Xu Wen Xiao Xiangui Meng Weiquan Li Xuegang Wang Xiaoping Zhang Hongmei Yang |
| author_facet | Ning Xu Wen Xiao Xiangui Meng Weiquan Li Xuegang Wang Xiaoping Zhang Hongmei Yang |
| author_sort | Ning Xu |
| collection | DOAJ |
| description | Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors of the urinary system. Distant metastasis is the leading cause of poor prognosis in ccRCC. However, ccRCC is found poorly responsitive to radiotherapy and chemotherapy. Effective therapeutic strategies for its metastasis remain scarce. We analyzed clinical samples and public database, for differential expression of SLC27A2 and further explored its relationship with clinical prognosis. Biochemistry and functional experiments were carried out to study the potential mechanisms of SLC27A2, CDK3, and EMT. SLC27A2 was significantly downregulated in clinical specimens and renal cancer cell lines and predicted poor prognosis. We found that specific upregulation of SLC27A2 could significantly inhibited the proliferation, migration, and invasion of renal cancer cell lines. SLC27A2 could also influence the Epithelial-mesenchymal transition (EMT) signaling pathway, linked to the progression and metastasis of renal cancer. Using whole transcriptome sequencing of SLC27A2, CDK3 was identified as a regulatory SLC27A2 target. In terms of mechanism, SLC27A2 may further inhibit the epithelial-to-mesenchymal transition by negatively regulating CDK3. Our work suggests that functional inhibition of SLC27A2-CDK3-EMT axis may be an attractive therapeutic target for metastasis of ccRCC. |
| first_indexed | 2024-12-10T21:44:20Z |
| format | Article |
| id | doaj.art-36cc3d47ea93439092b4ba73fbfb47cc |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-10T21:44:20Z |
| publishDate | 2022-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-36cc3d47ea93439092b4ba73fbfb47cc2022-12-22T01:32:24ZengNature Publishing GroupCell Death Discovery2058-77162022-08-018111210.1038/s41420-022-01145-8Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMTNing Xu0Wen Xiao1Xiangui Meng2Weiquan Li3Xuegang Wang4Xiaoping Zhang5Hongmei Yang6Department of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Urology, The First Affiliated Hospital, School of Medicine, Xiamen UniversityDepartment of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathogenic Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant tumors of the urinary system. Distant metastasis is the leading cause of poor prognosis in ccRCC. However, ccRCC is found poorly responsitive to radiotherapy and chemotherapy. Effective therapeutic strategies for its metastasis remain scarce. We analyzed clinical samples and public database, for differential expression of SLC27A2 and further explored its relationship with clinical prognosis. Biochemistry and functional experiments were carried out to study the potential mechanisms of SLC27A2, CDK3, and EMT. SLC27A2 was significantly downregulated in clinical specimens and renal cancer cell lines and predicted poor prognosis. We found that specific upregulation of SLC27A2 could significantly inhibited the proliferation, migration, and invasion of renal cancer cell lines. SLC27A2 could also influence the Epithelial-mesenchymal transition (EMT) signaling pathway, linked to the progression and metastasis of renal cancer. Using whole transcriptome sequencing of SLC27A2, CDK3 was identified as a regulatory SLC27A2 target. In terms of mechanism, SLC27A2 may further inhibit the epithelial-to-mesenchymal transition by negatively regulating CDK3. Our work suggests that functional inhibition of SLC27A2-CDK3-EMT axis may be an attractive therapeutic target for metastasis of ccRCC.https://doi.org/10.1038/s41420-022-01145-8 |
| spellingShingle | Ning Xu Wen Xiao Xiangui Meng Weiquan Li Xuegang Wang Xiaoping Zhang Hongmei Yang Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMT Cell Death Discovery |
| title | Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMT |
| title_full | Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMT |
| title_fullStr | Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMT |
| title_full_unstemmed | Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMT |
| title_short | Up-regulation of SLC27A2 suppresses the proliferation and invasion of renal cancer by down-regulating CDK3-mediated EMT |
| title_sort | up regulation of slc27a2 suppresses the proliferation and invasion of renal cancer by down regulating cdk3 mediated emt |
| url | https://doi.org/10.1038/s41420-022-01145-8 |
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