2. Academic Validation
  3. Sphingosine kinase 1 regulates lipid metabolism to promote progression of kidney renal clear cell carcinoma

Sphingosine kinase 1 regulates lipid metabolism to promote progression of kidney renal clear cell carcinoma

  • Pathol Res Pract. 2023 Aug;248:154641. doi: 10.1016/j.prp.2023.154641.
Leizuo Zhao 1,  Zicheng Wang 2,  Yingkun Xu 3,  Peizhi Zhang 4,  Jiechuan Qiu 5,  Dengke Nie 6,  Guangzhen Wu 7,  Chen Chen 8,  Yao Chang 5,  Qinghua Xia 9
Affiliations

Affiliations

  • 1 Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China; Department of Urology, Dongying People's Hospital, Dongying 257000, China.
  • 2 Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China; Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China.
  • 3 Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
  • 4 Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China.
  • 5 Department of Urology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China.
  • 6 Department of Chest Surgery, The First Affiliated Hospital of Henan University, Kaifeng 475001, China.
  • 7 Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
  • 8 Department of Urology, Liaocheng People's Hospital, Shandong University 252000, China.
  • 9 Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China. Electronic address: [email protected].
PMID: 37467634 DOI: 10.1016/j.prp.2023.154641
Abstract

Purpose: To detect the expression of sphingosine kinase 1 (SPHK1) in clear cell renal cell carcinoma (ccRCC) and explore its biological role in the occurrence and development of ccRCC through regulation of fatty acid metabolism.

Methods: Using the Cancer Genome Atlas database, SPHK1 expression and its clinical significance were detected in clear cell renal cell carcinoma. Immunohistochemistry was performed to detect SPHK1 expression in RCC samples in our hospital. The connection between the SPHK1 levels and clinicopathological features of patients was assessed. Nile Red was used to detect fatty acids in cells. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were performed to determine the effect of SPHK1 on renal cell viability and proliferation, respectively. Additionally, the effects of SPHK1 on the proliferation and metastasis of ccRCC were studied using wound healing and Transwell assays. Fatty acids were added exogenously in recovery experiments and western blotting was performed to determine the effect of SPHK1 on fatty acid metabolism in ccRCC. Finally, the effects of SPHK1 on tumor growth were investigated in a xenograft model.

Results: Bioinformatics analysis revealed that SPHK1 expression was upregulated in kidney RCC. OverSPHK1 expression was associated with poor prognosis for ccRCC patients. High SPHK1 expression was detected in human ccRCC. SPHK1 expression was related to clinicopathological features, such as tumor size and Furman grade. Additionally, cell proliferation, migration, and invasion were inhibited in ccRCC cells with low SPHK1 expression. In rescue experiments, proliferation, migration, and invasion were restored. In vivo, reduced SPHK1 levels correlated with lower expression of fatty acid synthase, stearoyl-CoA desaturase 1, and acetyl CoA carboxylase, and slowed tumor growth.

Conclusions: SPHK1 is abnormally overexpressed in human ccRCC. Patients with ccRCC may benefit from treatments that target SPHK1, which may also serve as a prognostic indicator.

Keywords

Clear cell renal cell carcinoma; Fatty acid metabolism; Progression; Sphingosine kinase 1; The Cancer Genome Atlas.

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