Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Emerging evidence has revealed that risk factors and metastatic patterns differ greatly between colon and rectal cancers. However, the molecular mechanism underlying their pathogenic differences remains unclear. Therefore, we here aimed to identify non-coding RNA biomarkers based on lncRNA-associated ceRNA network (LceNET) to elucidate the carcinogenic heterogeneity between colon and rectal cancers.
A global LceNET in human was constructed by employing experimental evidence-based miRNA-mRNA and miRNA-lncRNA interactions. Then, four context-specific ceRNA networks related to cancer initiation and metastasis were extracted by mapping differentially expressed lncRNAs, miRNAs and mRNAs to the global LceNET. Notably, a novel network-based bioinformatics model was proposed and applied to identify lncRNA/miRNA biomarkers and critical ceRNA triplets for understanding the carcinogenic heterogeneity between colon and rectal cancers. Moreover, the identified biomarkers were further validated by their diagnostic/prognostic performance, expression pattern and correlation analysis.
Based on network modeling, lncRNA KCNQ1OT1 (AUC>0.85) and SNHG1 (AUC>0.94) were unveiled as common diagnostic biomarkers for the initiation and metastasis of colon and rectal cancers. qRT-PCR analysis uncovered that these lncRNAs had significantly higher expression level in CRC cell lines with high metastatic potential. In particular, KCNQ1OT1 and SNHG1 function in colon and rectal cancers
The landscape of lncRNA-associated ceRNA network not only facilitates the exploration of non-coding RNA biomarkers, but also provides deep insights into the oncogenetic heterogeneity between colon and rectal cancers, thereby contributing to the optimization of diagnostic and therapeutic strategies of CRC.