PARP Inhibitor Olaparib Increases the Sensitivity of Breast Cancer Cells to DNA Damage by Inhibiting the Expression of LINP1

Abstract

Background: Breast cancer is a prevalent malignancy in women worldwide. Poly (ADP-ribose) polymerase (PARP)-1 and PARP-2 are critical for repair of DNA damage. In this study, we aimed to investigate whether PARP inhibitors can increase the sensitivity of breast cancer cells to DNA damage-based chemotherapy and radiotherapy and its related mechanisms. Methods: Quantitative-polymerase chain reaction (Q-PCR) was carried out to measure long non-coding RNA (lncRNA) in non-homologous end joining (NHEJ) pathway 1 (LINP1) expression in a breast cancer cell line and tumor tissue specimens collected from 23 patients with breast cancer. siRNAs for LINP1 and PARP were transfected to knockdown their expressions. The cell counting kit-8 (CCK-8) was used to measure cell survival. A wound-healing assay was used to assess the cell migration ability. Western blotting was used to measure the expression of DNA damage marker phosphorylated histone H2AX (γ-H2AX). Flow cytometry assay was used to measure the repair ability of non-homologous end joining (NHEJ) pathway in breast cancer cells. Results: The expression of the lncRNA LINP1 was significantly increased in both breast cancer tissues and Michigan Cancer Foundation-7 (MCF-7) cells (p < 0.01). Its expression was significantly reduced after treatment with a PARP inhibitor Olaparib (p < 0.01). After ultraviolet C (UV-C) irradiation, the expression of the DNA damage marker γ-H2AX was significantly increased in Olaparib-treated cancer cell, and the cell survival rate was significantly reduced (p < 0.01). However, cells treated with Olaparib and transfected with LINP1 plasmid effectively rescued their sensitivity to DNA damage and survival rate after irradiation. Conclusions: The PARP inhibitor Olaparib increases the sensitivity of breast cancer cells to DNA damage by reversely regulating the expression of LINP1.