Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma

doi:10.1186/s12885-023-11090-z

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Title:	Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma
Authors:	Liang, Peir-In Lai, Hong-Yue Chan, Ti-Chun Li, Wei-Ming Hsing, Chung-Hsi Huang, Steven K. K. Hsieh, Kun-Lin Tseng, Wen-Hsin Chen, Tzu-Ju Li, Wan-Shan Chen, Huan-Da Kuo, Yu-Hsuan Li, Chien-Feng
Contributors:	Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Pathol Chi Mei Med Ctr, Dept Med Res Natl Hlth Res Inst, Natl Inst Canc Res Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Urol Kaohsiung Med Univ, Coll Med, Sch Med, Dept Urol Kaohsiung Med Univ, Ctr Liquid Biopsy & Cohort Res Pingtung Hosp, Dept Urol, Minist Hlth & Welf Chi Mei Med Ctr, Dept Anesthesiol Chang Jung Christian Univ, Coll Hlth Sci, Dept Med Sci Ind Chi Mei Med Ctr, Dept Clin Pathol Chung Hwa Univ Med Technol, Dept Med Technol Chi Mei Med Ctr, Dept Pathol Chi Mei Med Ctr, Dept Internal Med, Div Hematol & Oncol Chia Nan Univ, Coll Pharm & Sci
Keywords:	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) Cellular Myelocytomatosis (C-Myc) Glucose transporter 1 (GLUT1) Metabolic process reprogramming
Date:	2023
Issue Date:	2024-12-25 11:03:42 (UTC+8)
Publisher:	BMC
Abstract:	BackgroundDihydropyrimidinase-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.MethodsA 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.ResultsThe 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.ConclusionsDPYSL3 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.
Relation:	Bmc Cancer, v.23, n.1, Article 599
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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