STAT3‐mediated gene expression in colorectal cancer cells‐derived cancer stem‐like tumorspheres

Abstract

STAT3 is a transcriptional factor involved in tumorigenesis and the initiation of cancer stemness property. However, the STAT3-downstream regulatory gene expressions in the formation of colorectal cancer (CRC)-derived tumorsphere is obscure.In this study, RNAseq was used to uncover the potential genes involved in the formation of colorectal HCT116-and HT29-derived stem-like tumorspheres, whereas HCT116 and HT29 overexpressed CD133. Furthermore, STAT3 was knockdowned and analyzed consequently by RNAseq for picking up the STAT3-mediated genes associated with tumorspheres formation. Then, quantitative polymerase chain reaction was used for validating the expressions of selected driver genes in epidermal growth factor (EGF) treated-and in STAT3-knockdowned HT29 cells. We found that 654 genes and 646 genes were upregulated in HCT116-and HT29-derived tumorspheres, respectively. There were 103 genes simultaneously increased in both CRC tumorspheres, including, STAT3 selected as a driver gene by NetworkAnalyst (https://www.networkanalyst.ca/). Moreover, there were 139 genes downregulated in HT29shSTAT3 cells compared to HT29shLuc cells, 12 of the genes were overlapped with the overexpressed 103 genes from tumorspheres, including, NDRG1,