BACKGROUND

is a member of the Kruppel-like factor, subfamily of zinc finger proteins that are involved in cancers. functions as a transcription factor and regulates the diverse protein-coding genes (PCGs) in colorectal cancer (CRC). However, the long non-coding RNAs (lncRNAs) regulated by in CRC are currently unknown.

METHODS

In this study, we first designed a computational pipeline to determine the PCG and lncRNA targets of in CRC. Then we analyzed the motif pattern of the binding regions for the lncRNA targets. The regulatory co-factors of were then searched for through bioinformatics analysis. We also constructed a regulatory network for and annotated its functions. Finally, one of the lncRNA targets, , was selected to further explore its expression pattern and functions in CRC.

RESULTS

We were able to identify 19 lncRNA targets of and found that the motifs of the lncRNA binding sites were GC-enriched. Next, we pinpointed the transcription factors and as the regulatory co-factors of through bioinformatics analysis. Then, through the analysis of the regulatory network, we found that may be involved in DNA replication, DNA repair, and the cell cycle. Furthermore, in the cell cycle module, the up-regulating expression pattern was verified in the CRC cell lines and tissues, associating it to CRC invasion and distal metastasis. This indicates that may play a critical part in CRC tumorigenesis and progression. Additionally, expression of was found to be down-regulated in CRC cell lines when expression was knocked-down by siRNA; and a strong correlation was observed between the expression levels of and , further alluding to their regulatory relationship.

CONCLUSIONS

In conclusion, the network analysis of targets indicates that may be a significant lncRNA in CRC.