Microarray Analysis of Long Non-coding RNA Expression Profile Associated with 5-Fluorouracil-Based Chemoradiation Resistance in Colorectal Cancer Cells


Background: Preoperative 5-fluorouracil (5-FU)-based chemoradiotherapy is a standard treatment for locallyadvanced colorectal cancer (CRC). However, CRC cells often develop chemoradiation resistance (CRR). Recentstudies have shown that long non-coding RNA (lncRNA) plays critical roles in a myriad of biological processesand human diseases, as well as chemotherapy resistance. Since the roles of lncRNAs in 5-FU-based CRR inhuman CRC cells remain unknown, they were investigated in this study. Materials and
Methods: A 5-FU-basedconcurrent CRR cell model was established using human CRC cell line HCT116. Microarray expression profilingof lncRNAs and mRNAs was undertaken in parental HCT116 and 5-FU-based CRR cell lines.
Results: In total,2,662 differentially expressed lncRNAs and 2,398 mRNAs were identified in 5-FU-based CRR HCT116 cellswhen compared with those in parental HCT116. Moreover, 6 lncRNAs and 6 mRNAs found to be differentiallyexpressed were validated by quantitative real time PCR (qRT-PCR). Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis for the differentially expressed mRNAs indicated involvement of many, such as Jak-STAT, PI3K-Akt and NF-kappa B signaling pathways. To better understand the molecular basis of 5-FU-basedCRR in CRC cells, correlated expression networks were constructed based on 8 intergenic lncRNAs and theirnearby coding genes.
Conclusions: Changes in lncRNA expression are involved in 5-FU-based CRR in CRCcells. These findings may provide novel insight for the prognosis and prediction of response to therapy in CRCpatients.