| Summary: | 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.
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