The expression of SLFN11 is related to the sensitivity of bladder cancer cells to DNA damage agents

Abstract

BackgroundPutative DNA/RNA helicase Schlafen-11 (SLFN11) was studied for its functions in cancer cells in current years, especially its ability of sensitizing cancer cells to DNA-damaging agents (DDA). However, little is known about the roles it plays in bladder cancer. MethodsBioinformatic tools including GEPIA, UALCAN, MEXPRESS, CTRP, cBioPortal, MethSurv, and Metascape were used. RT-qPCR, CCK-8 assay, and methylation specific PCR were used to verify the results of bioinformatic analysis in bladder cancer cells. ResultsCompared to the normal samples, the expression of SLFN11 was lower in BLCA samples. SLFN11 expression was associated with clinical parameters in BLCA patients, especially histological and molecular subtypes. Besides, its expression correlated to the sensitivity of cancer cells to DDA. Furthermore, the frequency of SLFN11 genetic alterations was low in BLCA patients, and methylationwas significantly negatively related to SLFN11 expression. The mRNA levels of SLFN11 in the bladder cancer cells UMUC-3, T24, and T24-GR were significantly lower than that in the normal SV-HUC-1 cells. SLFN11 expression was positively correlated with bladder cancer cells’ sensitivity to gemcitabine. In addition, partial methylation of SLFN11 was detected in T24-GR, and can be inhibited by 5-Aza. ConclusionsSLFN11 expression was lower in BLCA samples and in vitro bladder cancer cells than in the normal ones. The level of SLFN11 correlated to the sensitivity of cancer cells to DDA. Additionally, the methylation of SLFN11 was negatively related to its expression. It couldbe a potential prognostic biomarker for predicting the therapeutic effect of DNA-damaging agents in patients with bladder cancers.