CHD1L Accelerates Prostate Cancer Proliferation and Angiogenesis by Upregulating METAP2

Abstract

Background: Prostate cancer (PC) is a malignant tumor with higher death rate. Chromodomain-helicase-DNA-binding-protein 1-like (CHD1L) has been shown to be a key facilitator in cancers progression. High expression of methionine aminopeptidase 2 (METAP2) has been demonstrated in PC. However, the effects of CHD1L/METAP2 axis on PC progression are still undefined. Methods: The expressions of genes were confirmed by Real-Time quantitative Polymerase Chain Reaction (RT-qPCR), western bot or Immunohistochemistry (IHC) assay. Cell proliferation was tested by Cell counting kit-8 (CCK-8) and colony formation. Cell invasion and migration were examined using Transwell assay. The angiogenesis ability was assessed using tube formation. Tumor growth was evaluated in vivo assay. Results: CHD1L expression was up-regulated in the prostate adenocarcinoma (PRAD) tissues as compared to that in normal tissues using UALCAN and TIMER2.0 online websites. Further studies demonstrated that CHD1L exhibited higher mRNA and protein expression in PC tissues and cell lines. In addition, knockdown of CHD1L suppressed cell proliferation, migration and angiogenesis in PC. Positive correlation between CHD1L and METAP2 was shown in analysis based on TIMER2.0 and GEPIA online websites. Moreover, it was shown that CHD1L upregulated METAP2 expression in PC. METAP2 overexpression was shown to rescue the decreased cell proliferation, migration and angiogenesis mediated by CHD1L knockdown. Suppression of CHD1L was shown to inhibit tumor growth in vivo. Conclusions: Knockdown of CHD1L reduced PC cell proliferation, migration and angiogenesis through reducing METAP2. Our findings illustrated that the CHD1L/METAP2 axis may be useful bio-targets for PC treatment.