Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma
Abstract Background Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colo...
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BMC
2023-06-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-023-11090-z |
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| author | Peir-In Liang Hong-Yue Lai Ti-Chun Chan Wei-Ming Li Chung-Hsi Hsing Steven K. Huang Kun-Lin Hsieh Wen-Hsin Tseng Tzu-Ju Chen Wan-Shan Li Huan-Da Chen Yu-Hsuan Kuo Chien-Feng Li |
| author_facet | Peir-In Liang Hong-Yue Lai Ti-Chun Chan Wei-Ming Li Chung-Hsi Hsing Steven K. Huang Kun-Lin Hsieh Wen-Hsin Tseng Tzu-Ju Chen Wan-Shan Li Huan-Da Chen Yu-Hsuan Kuo Chien-Feng Li |
| author_sort | Peir-In Liang |
| collection | DOAJ |
| description | Abstract Background Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood. Methods A UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study. Results The in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression. Conclusions DPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC. |
| first_indexed | 2024-03-13T01:54:17Z |
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| id | doaj.art-39778566c92444fdb61b9cfb95990740 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-13T01:54:17Z |
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| spelling | doaj.art-39778566c92444fdb61b9cfb959907402023-07-02T11:18:18ZengBMCBMC Cancer1471-24072023-06-0123111710.1186/s12885-023-11090-zUpregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinomaPeir-In Liang0Hong-Yue Lai1Ti-Chun Chan2Wei-Ming Li3Chung-Hsi Hsing4Steven K. Huang5Kun-Lin Hsieh6Wen-Hsin Tseng7Tzu-Ju Chen8Wan-Shan Li9Huan-Da Chen10Yu-Hsuan Kuo11Chien-Feng Li12Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Medical Research, Chi Mei Medical CenterDepartment of Medical Research, Chi Mei Medical CenterDepartment of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Medical Research, Chi Mei Medical CenterDepartment of Surgery, Division of Urology, Chi Mei Medical CenterDepartment of Surgery, Division of Urology, Chi Mei Medical CenterDepartment of Surgery, Division of Urology, Chi Mei Medical CenterDepartment of Clinical Pathology, Chi Mei Medical CenterDepartment of Medical Technology, Chung Hwa University of Medical TechnologyDepartment of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical UniversityDepartment of Internal Medicine, Division of Hematology and Oncology, Chi-Mei Medical CenterDepartment of Medical Research, Chi Mei Medical CenterAbstract Background Dihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood. Methods A UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study. Results The in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression. Conclusions DPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC.https://doi.org/10.1186/s12885-023-11090-zDihydropyrimidinase-like 3 (DPYSL3)Upper urinary tracts urothelial carcinoma (UTUC)Urinary bladder urothelial carcinoma (UBUC)Cytoskeleton modificationMammalian target of rapamycin (mTOR)Ribosomal protein S6 (RPS6) |
| spellingShingle | Peir-In Liang Hong-Yue Lai Ti-Chun Chan Wei-Ming Li Chung-Hsi Hsing Steven K. Huang Kun-Lin Hsieh Wen-Hsin Tseng Tzu-Ju Chen Wan-Shan Li Huan-Da Chen Yu-Hsuan Kuo Chien-Feng Li Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma BMC Cancer Dihydropyrimidinase-like 3 (DPYSL3) Upper urinary tracts urothelial carcinoma (UTUC) Urinary bladder urothelial carcinoma (UBUC) Cytoskeleton modification Mammalian target of rapamycin (mTOR) Ribosomal protein S6 (RPS6) |
| title | Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma |
| title_full | Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma |
| title_fullStr | Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma |
| title_full_unstemmed | Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma |
| title_short | Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma |
| title_sort | upregulation of dihydropyrimidinase like 3 dpysl3 protein predicts poor prognosis in urothelial carcinoma |
| topic | Dihydropyrimidinase-like 3 (DPYSL3) Upper urinary tracts urothelial carcinoma (UTUC) Urinary bladder urothelial carcinoma (UBUC) Cytoskeleton modification Mammalian target of rapamycin (mTOR) Ribosomal protein S6 (RPS6) |
| url | https://doi.org/10.1186/s12885-023-11090-z |
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