Knockdown of CDX2 Induces microRNA-221 Up-regulation in Human Colon Cancer Cells

Abstract

Background/Aim: Caudal-type homeobox transcription factor 2 (CDX2) is a master regulator of intestinal development and maintenance of the intestinal epithelium. We previously revealed that CDX2^Low colorectal cancers (CRCs) were associated with poor survival and differential response to adjuvant chemotherapy. MicroRNAs (miRNAs), a class of non-coding RNAs typically composed of fewer than 25 nucleotides, are known to regulate gene expression and signaling pathways. This study aimed to identify oncogenic miRNAs induced by CDX2 in CRC. Materials and Methods: HCT116 cells were cultured and transfected with CDX2 siRNA. The expression levels of four oncogenic miRNAs (miR-9, miR-25, miR-106b and miR-221) were quantified by RT-qPCR. To understand whether CDX2 represented a key regulator of miR-221 expression in vivo, we analyzed the relationship between CDX2 and miR-221expression levels in the TCGA COAD database (n=454). Results: The expression level of miR-221 was significantly up-regulated in CDX2 knockdown cells (n=2, p<0.05). In the TCGA database, we observed an inverse correlation between CDX2 and miR-221 expression levels, consistent with our in vitro data (r=−0.114, p=0.0149). Furthermore, the expression level of miR-221 was significantly elevated in patients with CDX2^Low CRC (p<0.05). Conclusion: Knockdown of CDX2 induces microRNA-221 up-regulation in human CRC. Further research is warranted to elucidate the molecular mechanisms underlying miR-221 up-regulation in CDX2^Low CRCs.