DNA-Sensing and Nuclease Gene Expressions as Markers for Colorectal Cancer Progression

<b><i>Objective:</i></b> Oncogene-driven stress-related DNA damage has been observed in lesions of colon cancer. Furthermore, DNA sensors and nucleases are stimulated during active DNA damage and replication. However, their changes and influences with respect to cancer remain largely unknown. <b><i>Methods:</i></b> The gene expression levels of<i> cGAS</i>, <i>IFI16</i>, <i>STING</i>, <i>TBK1</i>, <i>IFNB1</i>, <i>TREX1</i>, <i>SAMHD1</i>, <i>RNASEH2A</i>, <i>RNASEH2B</i>, and<i> RNASEH2C</i> were examined in the paired colorectal cancer and adjacent normal part tissues of 53 patients. Their associations with the clinical stages of cancer were then analyzed. <b><i>Results:</i></b> All cytosolic DNA-sensing and nuclease-related genes except<i> cGAS</i>, <i>RNASEH2A</i>, and <i>RNASEH2B </i>showed lower mRNA expressions in the colorectal tumor tissues. Moreover, <i>cGAS</i> upregulation was found to be associated with early-stage colorectal cancers, while higher expressions of <i>RNASEH2B</i>, <i>RNASEH2C</i>, and <i>SAMHD1</i> correlated with metastasis. <i>RNASEH2C</i> knockdown in a colon cancer cell line impaired cell migration, and analysis of the cancer RNA-seq data from The Cancer Genome Atlas (TCGA) database revealed a negative correlation between <i>RNASEH2C</i> expression and E-cadherin levels. <b><i>Conclusions:</i></b> In contrast to DNA-sensing events in viral infections or autoimmunity, <i>cGAS</i>-<i>STING</i>-<i>IFNB</i> signaling is disrupted in colorectal cancer. The expression levels of <i>cGAS</i>, <i>RNASEH2B</i>, <i>RNASEH2C</i>, and <i>SAMHD1</i> could be prognostic markers of colorectal cancer.