Colorectal cancer (CRC) is the third most common cancer and the cause of cancer-related deaths worldwide. Due to the lack of highly sensitive and specific biomarkers, colorectal cancer often identified at the late stages in most patients when diagnosed. Identifying the potential cancer marker and understanding the mechanisms of metastasis and progression behind colorectal cancer is crucial for human CRC. Kynurenine 3-monooxygenase (KMO) is a monooxygenase participating in tryptophan metabolism. Previous studies showed that KMO related to metastasis and proliferation in hepatocellular carcinoma. However, the biological role of KMO in human CRC is still unclear.
The expression level of KMO in patients with CRC was examined using immunohistochemistry (IHC). The correlation between KMO expression and patient survival rate was analyzed using The Cancer Genome Atlas (TCGA) database. CRC cell lines were used to perform functional assays. UPF 648, a potent KMO inhibitor, and RNAi against KMO and luciferase were used for in vitro studies. Cell viability was analyzed by MTT assay. Cells motility was examined by transwell assay. Stemness properties were assessed by sphere assay and the expression of cancer stem cells markers.
IHC data showed that the expression of KMO was upregulated in CRC tumor tissues compared with normal counterparts of CRC. Furthermore, higher level of KMO transcript was associated with worse overall survival in CRC patients in TCGA database. Knockdown of KMO inhibited the expression of cancer stem cells markers, including CD44 and Nanog, as well as abilities of migration and invasion of CRC cells. Furthermore, the effect of KMO activity inhibition in cell viability was cell lines specific whereas the abilities of cell migration, invasion and sphere formation in CRC cells were significantly suppressed by UPF 648 treatment.
Our data suggests that KMO may serve as a potential biomarker and play tumor-promoting role in CRC.
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C. Liu, X. Mao: Employee of Burning Rock Biotech. All other authors have declared no conflicts of interest.