LINC02418 upregulates EPHA2 by competitively sponging miR-372-3p to promote 5-Fu/DDP chemoresistance in colorectal cancer.

ABSTRACT

Chemoresistance is a huge clinical challenge in the treatment of advanced colorectal cancer (CRC). Non-coding RNAs (ncRNAs) and messenger RNA (mRNA) are involved in CRC chemoresistance. However, the profiles of long ncRNAs (lncRNAs), microRNAs (miRNAs), mRNAs and competing endogenous RNA (ceRNA) networks in CRC chemoresistance are still largely unknown. Here, we compared the gene expression profiles in chemosensitive (HCT8) and chemoresistant [HCT8/5-fluorouracil (5-Fu) and HCT8/cisplatin (DDP)] cell lines by whole-transcriptome sequencing. The common differentially expressed RNAs in two drug-resistant cells were selected to construct lncRNA-miRNA-mRNA networks. The ceRNA network closely related to chemoresistance was further established based on the widely accepted drug resistance-associated genes enriched in three signaling pathways involved in chemoresistance. In total 52 lncRNA-miRNA-mRNA pathways were screened out, among which EPHA2 and LINC02418 were identified as hub genes; thus, LINC02418/miR-372-3p/EPHA2 were further selected and proved to affect the 5-Fu and DDP resistance of CRC. Mechanistically, LINC02418 upregulated EPHA2 by functioning as a 'sponge' of miR-372-3p to modulate the chemoresistance of CRC. Collectively, our study uncovered the underlying mechanism of LINC02418/miR-372-3p/EPHA2 in 5-Fu and DDP resistance of CRC, which may provide potential therapeutic targets for improving the chemosensitivity of CRC.