Abstract
BackgroundProstate cancer (PCa) is still a serious male malignant disease across the world. However, no exact pathogenesis had been explained. Although adenylosuccinate lyase (ADSL) gene was identified to be important in PCa early in 1987, its comprehensive functions for PCa have not been presented.MethodsThe cBioPortal for Cancer Genomics, Oncomine and GEO database were retrieved to investigate the associations between of the ADSL gene and PCa. Then, the PC-3, DU145 and C4-2B cell lines were applied in vitro experiments. RNA sequencing and further western blot (WB) were applied to explore the potential mechanisms of ADSL gene in PCa.ResultsBased on PCa clinical datasets, we firstly found ADSL gene highly expressed in PCa tissues. Moreover, its transcript level increased in the metastatic PCa further. Elevated ADSL gene expression indicated a poor prognosis of PCa. While inhibiting the expression of ADSL with siRNA, the ability of cell proliferation and migration all declined markedly, with increased cell apoptosis inversely. Most of cells were blocked in the G0/G1 phase. Additionally, RNA sequencing also discovered the inactivity of cell cycle pathway after ADSL knockdown, which had also confirmed on the proteins levels.ConclusionsOur study identified the ADSL as an oncogene of PCa through regulating the cell cycle pathway firstly, with explicit cell and clinical phenotypes. Further mechanisms were needed to confirm its carcinogenic effect.
Highlights
Prostate cancer (PCa) is the most common male malignant tumor around the world
adenylosuccinate lyase (ADSL) gene expression was significantly higher in the PCa (P < 0.05) than normal tissues, which hinted the potential carcinogenicity of ADSL (Fig. 1)
When collecting the clinical features (Gleason score, PSA level and tumor stage) and survival data, we excitedly found that high ADSL gene expression might shorten the time of metastasis-free survival (HR = 1.68 (1.12–2.52), P = 0.012) and biochemical (See figure on page.) Fig. 5 RNA-seq reveals inactivation of cell cycle pathway after ADSL knockdown. a Volcano plot of differentially expressed genes (DEGs) with 665 up-regulated expression genes after ADSL knockdown. b KEGG pathway analysis for the DEGs in the siADSL and control cell lines. c Gene set enrichment analysis (GSEA) analysis identified cell cycle pathway active in the control cell lines. d heat map presented many cell cycle related genes highly expressed in the control groups comparing to siADSL
Summary
Prostate cancer (PCa) is the most common male malignant tumor around the world. In 2018, GLOBOCAN estimated 1.3 million PCa and 359,000 associated deaths worldwide [1]. In 2019, 174,650 new cases and 31,620 deaths were estimated [2]. These data had been increased to 191,930 and 33,330 in 2020 [3]. Thereinto, adenylosuccinate lyase (ADSL) gene had been discovered to have potential role in PCa [4]. Prostate cancer (PCa) is still a serious male malignant disease across the world. Adenylosuccinate lyase (ADSL) gene was identified to be important in PCa early in 1987, its comprehensive functions for PCa have not been presented
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