hCINAP regulates the DNA damage response and mediates the resistance of acute myelocytic leukemia cells to therapy

Through RNA-seq of wildtype and hCINAP-deleted U2OS cells and whole genome bisulfite sequencing of the two U2OS cells, we show here that hCINAP is responsible for genomic stability and DNA damage response. Deletion of hCINAP directly decreased genomic stability and caused drug sensitivity. Also, when hCINAP is deleted, many genes are upregulated. These genes are involved in aging, DNA damage response and leukemia. In our wet lab experiment results, knockdown of hCINAP sensitizes a patient-derived xenograft (PDX) mouse model to chemotherapy. In clinical AML samples, low hCINAP expression is associated with a higher overall survival rate in patients. These results provide mechanistic insight into the function of hCINAP during the DNA damage response and its role in AML resistance to therapy. RNA-seq analysis was performed by ANNOROAD. Briefly, the total RNA from wild-type and knockout hCINAP U2OS cells was extracted, and sequences were performed with Illumina Solexa Ultrasequencing.