Abstract
As a class I carcinogen, arsenic has been reported to cause diseases accompanied by circRNAs regulating proliferation and apoptosis at the molecular level, but whether circP50 (circBase ID: hsa_circ_0008012) does the same has not been demonstrated. The aim of this study is to provide the basis for anti-lung cancer mechanism research, by studying the expression of circP50 under arsenic-induced conditions, and the effect and mechanism on the proliferation and apoptosis of A549 cells based on the circP50 knockdown models. To explore whether the circP50 is responsive to arsenic exposure, the qRT-PCR was applied to discover that the relative expression of circP50 in A549 cells increased only with increasing NaAsO2 dose and independent of its metabolites. We further determined the mechanism of circP50 by establishing circP50 knockdown models. The results of cell viability and EdU assays indicated the proliferation of A549 cells. According to the western blotting, phosphorylation of p53 at Ser15, Ser376, and Ser392 and acetylation of p53 at Lys370 and Lys382 were inhibited, resulting in the deficiency of p53 expression. Subsequently, the expression of genes downstream of p53 was reduced, including p21, PUMA, Caspase3, and Bcl-xS. Furthermore, the expressions of IKB-α, p65, and p50 decreased, but C-myc expression did not change significantly, referring to the NF-κB pathway was not dominant. The results suggest that circP50 mainly functions through the p53 pathway to mediate apoptosis in response to arsenic exposure.
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This work was supported by the National Natural Science Foundation of China (Grant No.82160607), Yunnan Applied Basic Research Projects-Union Foundation, Yunnan Provincial Science and Technology Department, and Kunming Medical University, China (Grant No.202101AY070001-054).
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Yizhu Mao wrote the first draft of the manuscript and all authors commented on previous versions of the manuscript; Yizhu Mao and Qian Zhou analyzed and interpreted the present study experiment and data; Jinhua Wang and Ruihuan Zhao performed material preparation; Xuefei Yang, Ya Shi and Jinyao Yin collected and analyzed data; Chenglan Jiang prepared the instrument for the experiment; Yuefeng He had the idea for the article and revised the first version of the manuscript. All authors read and approved the final manuscript.
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Mao, Y., Zhou, Q., Wang, J. et al. CircP50 functions through the phosphorylation- and acetylation-activated p53 pathway to mediate inorganic arsenic-induced apoptosis in A549 cells. Environ Sci Pollut Res 29, 91232–91240 (2022). https://doi.org/10.1007/s11356-022-22094-w
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DOI: https://doi.org/10.1007/s11356-022-22094-w