Long noncoding RNA and mRNA profiling in cetuximab-resistant colorectal cancer cells by RNA sequencing analysis.

ABSTRACT

To gain an insight into the molecular mechanisms of cetuximab resistance in colorectal cancer, we generated a cetuximab-resistant cell line (H508/CR) and performed RNA sequencing to identify the differential expression patterns of noncoding RNAs (ncRNAs) and mRNAs between cetuximab-sensitive and resistant cells. A total of 278 ncRNA transcripts and 1,059 mRNA transcripts were dysregulated in the cetuximab-resistant cells. The expression levels of nine selected long noncoding RNAs (lncRNAs) were validated using quantitative real-time PCR. Functional analysis revealed that several groups of lncRNAs might be involved in pathways associated with cetuximab resistance. Increased glucose consumption and lactate secretion in cetuximab-resistant cells suggested that glucose metabolism might be involved in cetuximab resistance. In addition, lncRNA LINC00973 was upregulated in the H508/CR cell line and cells transfected with a LINC00973 short interfering RNA exhibited reduced cell viability, increased apoptosis, and decreased glucose consumption and lactate secretion. Our results provide essential data regarding differentially expressed lncRNAs and mRNAs in cetuximab-resistant cells, which may provide new potential candidates for cetuximab therapy.