Abstract: Background and purpose: Breast cancer is the most commonly diagnosed cancer, but its underlying mechanism remains elusive. The previous studies have demonstrated that ring finger protein 144A (RNF144A) regulates the stablity of poly (ADPribose) polymerase 1 (PARP1) and thus affects the sensitivity of breast cancer cells to PARP inhibitor olaparib. This study was designed to investigate whether PARP1 could regulate RNF144A and its effect on apoptosis of breast cancer cells following treatment with olaparib. Methods: Expression levels of PARP1 in breast cancer tissues were detected by immunohistochemistry, and the relationship between PARP1 expression levels and prognosis of breast cancer patients was analyzed. The effects of overexpression or knockdown of PARP1 on RNF144A protein and mRNA expression were detected by Western blot and real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR), respectively. Annexin Ⅴ-PE/7-AAD double staining was used to detect apoptosis by flow cytometry. Results: The positive rate of PARP1 expression was 68% in normal breast tissues, and patients with high expression of PARP1 had poor prognosis. Modulation of PARP1 negatively regulated RNF144A at the protein but not mRNA level. Overexpression of PARP1 enhanced anti-apoptotic effect of cells following olaparib treatment. Moreover, introduction of RNF144A in PARP1 overexpressing cells rescued the anti-apoptotic effects of PARP1 overexpression in breast cancer cells following olaparib treatment. Conclusion: The expression levels of PARP1 are associated with the prognosis of breast cancer patients, and PARP1 may play an oncogenic role in the development and progression of breast cancer. PARP1 negatively regulates RNF144A at the protein level without affecting its transcription. PARP1 inhibits apoptosis of breast cancer cells partially through regulating RNF144A.

Key words: Breast cancer, PARP1, Prognosis, RNF144A, Apoptosis