Objective: Our study aimed to evaluate the effect of circular RNA ABCB10 (circ-ABCB10) on proliferation and apoptosis of clear cell renal cell carcinoma (ccRCC) cells, and its prognostic value in patients with ccRCC. Methods: Circ-ABCB10 expression in five ccRCC cell lines and normal kidney epithelial cell line was measured by quantitative polymerase chain reaction (qPCR). Empty overexpression, circ-ABCB10 overexpression, empty shRNA, and circ-ABCB10 shRNA plasmids were transfected into A498 cells as negative control for circ-ABCB10 over expression {NC (+)}, Circ-ABCB10(+), negative control (−){NC(−)}, and Circ-ABCB10(−) groups, then cell proliferation and apoptosis were evaluated by Cell Counting Kit-8 and annexin V/propidium iodide. Meanwhile, apoptotic markers were measured by western blot. Subsequently, circ-ABCB10 expression in tumor tissues and paired adjacent tissues from 120 ccRCC patients was measured by qPCR. Results: Circ-ABCB10 expression was elevated in all the ccRCC cell lines compared with the normal kidney cells line. A498 cell proliferation was enhanced in the Circ-ABCB10(+) group compared with the NC(+) group, while it was inhibited in the Circ-ABCB10(−) group compared with the NC (−) group; and A498 cell apoptosis was repressed in the Circ-ABCB10(+) group than the NC(+) group, but was promoted in the Circ-ABCB10(−) group compared with the NC(−) group. In addition, circ-ABCB10 was up-regulated in tumor tissues compared with paired adjacent tissues, and its high expression correlated with the advanced pathological grade and the tumor node metastasis stage as well as independently predicting worse overall survival in ccRCC patients. Conclusion: Circ-ABCB10 promotes tumor progression and correlates with pejorative prognosis in ccRCC.

Cancer cells typically experience higher oxidative stress than normal cells, such that elevating pro-oxidant levels can trigger cancer cell death. Although pre-exposure to mild oxidative agents will sensitize cancer cells to radiation, this pre-exposure may also activate the adaptive stress defense system in normal cells. Ascorbic acid (AA) is a prototype redox modulator that when infused intravenously appears to kill cancers without injury to normal tissues; however, the mechanisms involved remain elusive. In this study, we show how AA kills cancer cells and sensitizes prostate cancer to radiation therapy, while also conferring protection upon normal prostate epithelial cells against radiation-induced injury. We found that the NF-κB transcription factor RelB is a pivotal determinant in the differential radiosensitization effects of AA in prostate cancer cells and normal prostate epithelial cells. Mechanistically, high ROS concentrations suppress RelB in cancer cells. RelB suppression decreases expression of the sirtuin SIRT3 and the powerful antioxidant MnSOD, which in turn increases oxidative and metabolic stresses in prostate cancer cells. In contrast, AA enhances RelB expression in normal cells, improving antioxidant and metabolic defenses against radiation injury. In addition to showing how RelB mediates the differential effects of AA on cancer and normal tissue radiosensitivities, our work also provides a proof of concept for the existence of redox modulators that can improve the efficacy of radiotherapy while protecting against normal tissue injury in cancer settings.

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