BACKGROUND: Oncogenic KRAS signaling is dysregulated in a three-dimensional (3D)-specific manner in human colorectal cancer (CRC) HCT116 cells. However, the identity of the crucial genes which are down-regulated through oncogenic KRAS in 3D cultures remains unclear. MATERIALS AND METHODS: We established a specific anti-alpha-kinase 2 (ALPK2) antibody and addressed the ALPK2 function in HKe3 cells, which are HCT116 cells with a disruption in oncogenic KRAS, in a 3D colonic-crypt model. RESULTS: In HKe3 cells grown in 3D culture, ALPK2 siRNA inhibited luminal apoptosis and reduced the expression of cleaved caspase-3. Furthermore, ALPK2 siRNA reduced the expression of DNA repair genes. Reduced expression of ALPK2 mRNA was found to be correlated with clinical colorectal adenomas in a public dataset of gene expression analyses. CONCLUSION: ALPK2, down-regulated by oncogenic KRAS, is crucial for luminal apoptosis and expression of DNA repair-related genes, possibly in the transition of normal colonic crypt to adenoma.
BACKGROUND: Oncogenic KRAS signaling is dysregulated in a three-dimensional (3D)-specific manner in humancolorectal cancer (CRC) HCT116 cells. However, the identity of the crucial genes which are down-regulated through oncogenic KRAS in 3D cultures remains unclear. MATERIALS AND METHODS: We established a specific anti-alpha-kinase 2 (ALPK2) antibody and addressed the ALPK2 function in HKe3 cells, which are HCT116 cells with a disruption in oncogenic KRAS, in a 3D colonic-crypt model. RESULTS: In HKe3 cells grown in 3D culture, ALPK2 siRNA inhibited luminal apoptosis and reduced the expression of cleaved caspase-3. Furthermore, ALPK2 siRNA reduced the expression of DNA repair genes. Reduced expression of ALPK2 mRNA was found to be correlated with clinical colorectal adenomas in a public dataset of gene expression analyses. CONCLUSION:ALPK2, down-regulated by oncogenic KRAS, is crucial for luminal apoptosis and expression of DNA repair-related genes, possibly in the transition of normal colonic crypt to adenoma.
Authors: Peter Hofsteen; Aaron Mark Robitaille; Nicholas Strash; Nathan Palpant; Randall T Moon; Lil Pabon; Charles E Murry Journal: iScience Date: 2018-04-27
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