Abstract
Accumulating evidence highlights the role of long non-coding RNAs (lncRNAs) in tumors. However, the genome-wide expression and roles of lncRNAs in colorectal cancer (CRC) remain unknown. Here, we systematically examined the global gene expressions in primary and synchronous liver metastases CRC tissue, in which thousands of aberrantly expressed lncRNAs were characterized. Co-expression analysis revealed that some lncRNAs correlated to their neighboring mRNAs in expression levels, whereas others formed networks with protein-coding genes in trans. We observed H3K4me3 was enriched at expressed lncRNA transcription start sites (TSSs) and correlated to dysregulated lncRNAs. Furthermore, we identified primary and metastasis tumor linked lncRNA signatures positively correlated with poor-prognosis gene set. Finally, functional experiments demonstrated two candidate lncRNAs were required for proliferation and migration of CRC cells. In summary, we provided a new framework for lncRNA associated clinical prognosis evaluation and target selection of gene therapy in CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer related death worldwide, which has been a great threat to public health
In agreement with previous observations that long non-coding RNAs (lncRNAs) exhibited greater tissue specificity in expression than mRNAs [9], our results suggested that lncRNAs could show disease stage specific expression patterns compared to protein-coding genes in CRC
We presented the first report on lncRNA expression landscape in patients with matched primary tumor and synchronous liver metastases
Summary
Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer related death worldwide, which has been a great threat to public health. Studies on transcriptional regulatory networks [3] and epigenetics such as microRNAs [4, 5], DNA methylation [6] and enhancer elements [7] in CRC have emerged. Accumulating evidence suggested that thousands of lncRNAs existed and exhibited highly tissue and cell-type specific manner [9]. Despite do not encode protein, lncRNAs have been proved to be involved in diverse physiological and pathological processes, such as cell growth, apoptosis, stem cell pluripotency, development and cancer biology by acting as transcriptional, posttranscriptional, or epigenetic regulators [10, 11]. A panel of tumor-type specific differentially expressed lncRNAs are identified and some of which have been functionally verified to contribute to tumorgenesis or serve as putative diagnostic markers
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