PARP-1 inhibits DNMT1-mediated promoter methylation and promotes linc01132 expression in benzene-exposed workers and hydroquinone-induced malignant transformed cells

Abstract

Hydroquinone (HQ), one of the main active metabolites of benzene, can induce the abnormal expression of long non-coding RNA (lncRNA). Studies have shown that lncRNA plays an important role in the occurrence of hematologic tumors induced by benzene or HQ. However, the molecular mechanism remains to be elucidated. Here, we investigated the molecular mechanism by which poly(ADP-ribose)polymerase 1 (PARP-1) interacts with DNA methyltransferase 1 (DNMT1) to regulate promoter methylation mediated linc01132 expression in HQ-induced TK6 malignant transformed cells (HQ-MT). The results revealed that the expression of linc01132 was increased in benzene-exposed workers and HQ-MT cells. The methylation of linc01132 promoter region was inhibited. Furthermore, in HQ-MT cells treated with 5-Aza-2′-deoxycytidine (5-AzaC) (DNA methyltransferase inhibitor) or trichostatin A (TSA) (histone deacetylation inhibitor), the expression of linc01132 was increased due to the regulation of DNA promoter methylation level by inhibiting DNMT1 expression. The methylation level of linc01132 promoter was correlated negatively with the expression of linc01132 in benzene-exposed workers, indicating that DNA methylation may contribute the expression of linc01132. Knockout of DNMT1, not DNMT3b, increased the expression of linc01132 as well as the demethylation of linc01132 promoter in HQ-MT cells. It was found that by knockdown PARP-1, the expression of DNMT1 in the nucleus was increased by immunofluorescence confocal microscopy, leading to the inhibition of hypermethylation in the promoter region of linc01132. Therefore, PARP-1 inhibits DNA methyltransferase (DNMT)-mediated promoter methylation and plays a role in linc01132 expression in benzene-exposed workers or HQ-MT cells, and is associated with benzene or HQ induced leukemia progression.

Keywords:

• Benzene
• hydroquinone
• linc01132
• DNMT1
• PARP-1

Author contributions

Haiqiao Zhang and Fengzhi Jiang: conceptualization, methodology, validation, investigation, data curation, and writing – original draft. Xiaoxuan Ling: methodology, validation, and editing. Bohuan Zhong: conceptualization and validation. Yali Han: methodology and data analysis. Zhijie Pan: methodology, validation and visualization. Qian Yuan: formal analysis. Jinxue Meng: resources, investigation, and questionnaire design. Dongyan Zheng: formal analysis. Xiaobing Chen and Qinghua Zhong: methodology. Linhua Liu: resources, writing – review and editing, project administration, and funding acquisition.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [82204134], the Natural Science Foundation of Guangdong Province [2022A1515140180, 2020A1515110614], the Medical Scientific Research Funding of Guangdong Province, China [A2020189], and the Discipline Construction Project of Guangdong Medical University [4SG22260G].