Shujian Xu1,2, Cui Zhao3, Zhongming Jia2, Xilong Wang2, Yong Han2, Zhenlin Yang4. 1. Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, 250012, China. 2. Department of Thyroid and Breast Surgery, The Affiliated Hospital to Binzhou Medical University, No. 661, Huangheer Road, Bincheng District, Binzhou, 256603, China. 3. Department of Rehabilitation Medicine, The Affiliated Hospital to Binzhou Medical University, Binzhou, 256603, China. 4. Department of Thyroid and Breast Surgery, The Affiliated Hospital to Binzhou Medical University, No. 661, Huangheer Road, Bincheng District, Binzhou, 256603, China. yangzhenlin6609@126.com.
Abstract
PURPOSE: Breast cancer is the most common invasive type of cancer among women. Role of different microRNAs (miRNAs) and poly(ADP-ribose) polymerases (PARPs) in breast cancer has been well established. This study aimed to explore the effects of miR-891b on sensitizing breast cancer cells to alkylating chemotherapeutic drugs through PARPs. METHODS: The expression of miR-891b and PARP1 in human breast cancer cells HCC1806 was overexpressed by transfection with their mimics or expressing vector. Then, the transfected cells were exposed to 40 µM N-methyl-N-nitro-N-nitrosoguanidine (MNNG) for 1 h. The correlation between miR-891b and PARP1 was detected by RT-qPCR, western blot, and dual-luciferase reporter assay. Besides, MTT assay and Annexin V assay were done to measure cell proliferation and apoptosis, respectively. RESULTS: PARP1 was a target of miR-891b, and it was negatively regulated by miR-891b. MiR-891b increased the sensitivity of the HCC1806 cells to the cytotoxic effects of MNNG through suppressing cell proliferation and increasing the percentage of apoptotic cells. Restoration of PARP1 activity in the HCC1806 cells led to loss of miR-891b mediated sensitivity of the HCC1806 cells to MNNG. CONCLUSION: MiR-891b increases the sensitivity of the breast cancer cells (HCC1806) to the cytotoxic effects of the chemotherapeutic agent MNNG by suppressing the expression of PARP1.
PURPOSE:Breast cancer is the most common invasive type of cancer among women. Role of different microRNAs (miRNAs) and poly(ADP-ribose) polymerases (PARPs) in breast cancer has been well established. This study aimed to explore the effects of miR-891b on sensitizing breast cancer cells to alkylating chemotherapeutic drugs through PARPs. METHODS: The expression of miR-891b and PARP1 in humanbreast cancer cells HCC1806 was overexpressed by transfection with their mimics or expressing vector. Then, the transfected cells were exposed to 40 µM N-methyl-N-nitro-N-nitrosoguanidine (MNNG) for 1 h. The correlation between miR-891b and PARP1 was detected by RT-qPCR, western blot, and dual-luciferase reporter assay. Besides, MTT assay and Annexin V assay were done to measure cell proliferation and apoptosis, respectively. RESULTS:PARP1 was a target of miR-891b, and it was negatively regulated by miR-891b. MiR-891b increased the sensitivity of the HCC1806 cells to the cytotoxic effects of MNNG through suppressing cell proliferation and increasing the percentage of apoptotic cells. Restoration of PARP1 activity in the HCC1806 cells led to loss of miR-891b mediated sensitivity of the HCC1806 cells to MNNG. CONCLUSION:MiR-891b increases the sensitivity of the breast cancer cells (HCC1806) to the cytotoxic effects of the chemotherapeutic agent MNNG by suppressing the expression of PARP1.
Entities:
Keywords:
Alkylating chemotherapeutic agent; Breast cancer; MNNG; MicroRNA-181b; PARP1