Regulation of Tumor-induced Platelet Clearance Modulated by the ERCC Family Through Mitochondrial Pathway

Thrombocytopenia, a common complication among patients with solid tumors, can be life-threatening when it leads to thrombosis. Although routine and frequent transfusion of blood components to those patients effectively improves the outcome of treatment, it brings a huge cost and burden to the health care system. Apoptosis mediated by intrinsic mitochondrial pathways has been well described in platelet clearance in vivo. However, the biological mechanism of thrombocytopenia modulated by mitochondria in tumor patients is unclear. In this paper, the expressions of the excision repair cross-complementing (ERCC) family, a set of proteins in DNA damage repair, are investigated by a bioinformatics analysis. The results presented that the mRNA expression level of 5 genes in the ERCC family has been significantly decreased in platelets from six different tumor patients versus healthy donors. There were no patterns of the downregulation of the ERCC family correlating to specific tumor types among the six test samples. In nucleated cells, cell death mediated by the intrinsic apoptotic pathway occurs when ROS overproduction demolishes the mitochondrial integrity and damages the mitochondrial DNA (mtDNA). Given platelets are anucleate, the expression of the ERCC family to target mtDNA repair is hypothesized.