Abstract
BackgroundThe sterile alpha motif (SAM) domain and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) has been specifically linked to lung cancer. However, the underlying mechanisms in regulating lung adenocarcinoma (LAC) are unclear. The aim of this study was to assess the specific regulation between SAMHD1 and LAC.MethodsWe retrospectively reviewed 238 patients who underwent surgery for LAC between January 2018 and December 2019. The expression of SAMHD1 was detected by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) in tumors and paired adjacent tissues. A lentivirus was used to overexpress SAMHD1 and stimulator of interferon genes (STING) in A549 cells; and RT-qPCR and western blot analysis were performed to verify their levels. Cell proliferation was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Celigo imaging cytometry. Cell apoptosis was detected by Annexin V staining. Overexpressed SAMHD1 suppressed LAC progression in a xenograft model. The DNA damage response inhibitor (DDRi) was used to assess the cell proliferation and apoptosis rate in SAMHD1-overexpressing A549 cells and the control group. A rescue experiment was carried out to evaluate the potential influence of SAMHD1 and STING.ResultsA low expression of SAMHD1 was associated with advanced disease. Overexpression of SAMHD1 decreased cell proliferation and invasion in A549 cells, and the apoptosis rate was significantly higher in the overexpressed SAMHD1 cells than those in the control group. The overexpression of SAMHD1 inhibited tumor progression in the xenograft model. The expression of STING was lower in SAMHD1-overexpressing A549 cells than those in the wild-type group. Furthermore, the inhibited cellular behaviors of LAC cells resulting from the stable SAMHD1 expression were partially reversed after STING overexpression. Treatment with DDRi could inhibit cancer cell progression.ConclusionsUpregulation of SAMHD1 could suppress the progression of LAC in vivo and in vitro through the negative regulation of STING.
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