Hsa_circ_0001944 regulates apoptosis by regulating the binding of PARP1 and HuR in leukemia and malignant transformed cells induced by hydroquinone

Environ Toxicol. 2022 Nov 30. doi: 10.1002/tox.23719. Online ahead of print.

ABSTRACT

Hydroquinone (HQ) is one of the major metabolites of benzene and can cause abnormal gene expression. It is a known carcinogen that alters cell cycle disruption and cell proliferation. However, its chemical mechanism remain a mystery. Circular RNAs (circRNAs) are a subtype of noncoding RNAs (ncRNAs) that play a variety of roles in biological processes. Hsa_circ_001944 expression was upregulated in 30 leukemia patients and HQ-induced malignant transformed TK6 cells. Hsa_circ_001944 silencing inhibited the growth of HQ-TK6 cells and halted the cell cycle. The silencing of hsa_circ_0001944 led to increased cell accumulation in G1 versus S phase, increased apoptosis in the sh1944 versus the shNC group, and increased levels of DNA damage (γ-H2AX), leading to cell cycle arrest. In summary, inhibition of hsa_circ_001944 restricted cell growth by inhibiting cell cycle arrest and induced growth of HQ-TK6 cells by modulating PARP1 expression. Hsa_circ_0001944 targeted HuR, which is a kind of RNA-binding protein, to control PARP1 expression via RNAinter, RBPmap, and RBPdb. Fluorescence in situ hybridization combined with immunofluorescent labeling and western blotting experiments showed that hsa_circ_001944 was able to dissociate HuR and PARP1 binding in HQ-TK6 cells, control PARP1 production, and ultimately alter the PARP1/H-Ras pathway.

PMID:36448377 | DOI:10.1002/tox.23719

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