Colorectal liver metastases-specific lncRNA CRLM1 inhibits apoptosis and promotes metastasis through transcriptional regulation cooperated with hnRNPK [CRLM1_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. Overall design: To further explore the biological functions of lncRNA-CRLM1 in colorectal cancer cells, we established a HCT116 cell line with stable CRLM1 overexpression (CRLM1-OE). Two negative control cell lines were prepared in parallel, including empty plasmid (Ctrl) and plasmid with CRLM1 antisense sequences (CRLM1-anti, see methods for detail information). Three biological replicates were prepared for each sample.