Colorectal liver metastases-specific lncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK [HNRNPK_OE]

The survival rate of colorectal liver metastases remains low. Long noncoding lncRNAs is emerging as a novel class of master regulators of cell invasion and metastasis. In this study, analysis of the lncRNA expression dynamics in the colorectal liver metastases, primary colorectal tumor and normal tissues led to the identification of the metastasis-specific expression of a set of lncRNAs including CRLM1. CRLM1 inhibited apoptosis and promoted metastasis and invasion of colorectal cancer cells, and also promoted tumor growth in nude mice. CRLM1 weakly associated with chromatin regions of genes involved in cell adhesion and DNA damage, correlated with CRLM1-regulated gene expression bidirectionally. CRLM1 physically interacts with and promotes the nuclear localization of the metastasis protein hnRNPK. CRLM1 effectively promotes hnRNPK promoter occupancy, and co-regulate gene expression. These findings suggest a potential biomarker and druggable target for treatment of colorectal liver metastases. We overexpressed hnRNPK in HCT116 cells with stable overexpression of lncRNA-CRLM1 and in those without (antisense control and empty control). Transcriptome sequencing (RNA-seq) was conducted to identify CRLM1 and hnRNPK regulated genes. Three biological replicates were prepared for each sample