High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10
Abstract Background Clear cell renal cell carcinoma (ccRCC), the most common urological malignancy, has an unfavorable prognosis and an unknown mechanism of progression. Through survival analyses screening of The Cancer Genome Atlas (TCGA) dataset, we identified Visual system homeobox1 (VSX1) as a n...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03772-2 |
| _version_ | 1811311025087053824 |
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| author | Wenliang Ma Xin Li Lei Yang Jun Pan Yi Chen Yanwen Lu Xiang Dong Dongmei Li Weidong Gan |
| author_facet | Wenliang Ma Xin Li Lei Yang Jun Pan Yi Chen Yanwen Lu Xiang Dong Dongmei Li Weidong Gan |
| author_sort | Wenliang Ma |
| collection | DOAJ |
| description | Abstract Background Clear cell renal cell carcinoma (ccRCC), the most common urological malignancy, has an unfavorable prognosis and an unknown mechanism of progression. Through survival analyses screening of The Cancer Genome Atlas (TCGA) dataset, we identified Visual system homeobox1 (VSX1) as a novel potential prognostic biomarker in ccRCC and subsequently investigated the oncogenic role of VSX1 in ccRCC. Methods The differential expression of VSX1 in human tumors and the clinical prognoses were analyzed in the TCGA dataset and Gene Expression Omnibus. Spearman’s correlation coefficient was determined for the correlation analysis of VSX1 expression and other genes of interest. The roles of VSX1 in cell proliferation, invasion, and migration of ccRCC cells were evaluated via the CCK-8 assay, colony formation assay, and Transwell assay, respectively. Further results were demonstrated by western blotting, immunohistochemistry, qRT-PCR, tumor sphere formation, flow cytometry, and the dual‑luciferase reporter assay. Results VSX1 mRNA upregulation was generally observed in multiple human malignancies from the TCGA database and was confirmed in ccRCC clinical specimens from our department. High VSX1 expression usually indicated that overall and disease-free survival were unfavorable for patients with ccRCC. In terms of mechanism, knockdown or overexpression of VSX1 affected ccRCC aggressiveness in vitro. The dual-luciferase reporter gene assay implied that VSX1 overexpression significantly increased the luciferase activity of TMEM44, FKBP10, and TRIB3, which indicated that VSX1 promoted ccRCC invasiveness via transcriptional regulation of these genes. The significantly enhanced growth in vitro that was induced by stable VSX1 overexpression was almost restored to normal by the knockdown of FKBP10. Conclusions This study demonstrated that VSX1 was a novel prognostic biomarker in ccRCC and that high VSX1 expression promoted cell proliferation, invasion, and migration in ccRCC via transcriptional activation of downstream target genes. |
| first_indexed | 2024-04-13T10:10:33Z |
| format | Article |
| id | doaj.art-3b357ea8fdbe4347be8de431eecc8905 |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-13T10:10:33Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj.art-3b357ea8fdbe4347be8de431eecc89052022-12-22T02:50:55ZengBMCJournal of Translational Medicine1479-58762022-12-0120111510.1186/s12967-022-03772-2High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10Wenliang Ma0Xin Li1Lei Yang2Jun Pan3Yi Chen4Yanwen Lu5Xiang Dong6Dongmei Li7Weidong Gan8Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityImmunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing UniversityImmunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing UniversityDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityImmunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing UniversityDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityImmunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing UniversityDepartment of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing UniversityAbstract Background Clear cell renal cell carcinoma (ccRCC), the most common urological malignancy, has an unfavorable prognosis and an unknown mechanism of progression. Through survival analyses screening of The Cancer Genome Atlas (TCGA) dataset, we identified Visual system homeobox1 (VSX1) as a novel potential prognostic biomarker in ccRCC and subsequently investigated the oncogenic role of VSX1 in ccRCC. Methods The differential expression of VSX1 in human tumors and the clinical prognoses were analyzed in the TCGA dataset and Gene Expression Omnibus. Spearman’s correlation coefficient was determined for the correlation analysis of VSX1 expression and other genes of interest. The roles of VSX1 in cell proliferation, invasion, and migration of ccRCC cells were evaluated via the CCK-8 assay, colony formation assay, and Transwell assay, respectively. Further results were demonstrated by western blotting, immunohistochemistry, qRT-PCR, tumor sphere formation, flow cytometry, and the dual‑luciferase reporter assay. Results VSX1 mRNA upregulation was generally observed in multiple human malignancies from the TCGA database and was confirmed in ccRCC clinical specimens from our department. High VSX1 expression usually indicated that overall and disease-free survival were unfavorable for patients with ccRCC. In terms of mechanism, knockdown or overexpression of VSX1 affected ccRCC aggressiveness in vitro. The dual-luciferase reporter gene assay implied that VSX1 overexpression significantly increased the luciferase activity of TMEM44, FKBP10, and TRIB3, which indicated that VSX1 promoted ccRCC invasiveness via transcriptional regulation of these genes. The significantly enhanced growth in vitro that was induced by stable VSX1 overexpression was almost restored to normal by the knockdown of FKBP10. Conclusions This study demonstrated that VSX1 was a novel prognostic biomarker in ccRCC and that high VSX1 expression promoted cell proliferation, invasion, and migration in ccRCC via transcriptional activation of downstream target genes.https://doi.org/10.1186/s12967-022-03772-2VSX1Clear cell renal cell carcinomaMigrationInvasionTranscriptional regulation |
| spellingShingle | Wenliang Ma Xin Li Lei Yang Jun Pan Yi Chen Yanwen Lu Xiang Dong Dongmei Li Weidong Gan High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10 Journal of Translational Medicine VSX1 Clear cell renal cell carcinoma Migration Invasion Transcriptional regulation |
| title | High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10 |
| title_full | High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10 |
| title_fullStr | High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10 |
| title_full_unstemmed | High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10 |
| title_short | High VSX1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating FKBP10 |
| title_sort | high vsx1 expression promotes the aggressiveness of clear cell renal cell carcinoma by transcriptionally regulating fkbp10 |
| topic | VSX1 Clear cell renal cell carcinoma Migration Invasion Transcriptional regulation |
| url | https://doi.org/10.1186/s12967-022-03772-2 |
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