Tumor suppressor p53 induces miR-15a processing to inhibit neuronal apoptosis inhibitory protein (NAIP) in the apoptotic response DNA damage in breast cancer cell.
This study was aimed to investigate the functional role of miR-15a in breast cancer cells in response to DNA damage and to illustrate the possible potential underlying molecular mechanism(s). Human breast cancer cell lines MCF-7 cells and/or MDA-MB-231 cells were pre-treated with or without bleomycin. Cells were transfected with corresponding vectors. qRT-PCR was used to detect the expression of mRNA or miRNA, and immunoprecipitation and immunoblot analysis were performed to explore the status of protein association. Cell apoptosis was analyzed with flow cytometry. The results showed that neuronal apoptosis inhibitory protein (NAIP) was negatively regulated by p53 in MCF-7 cells, and NAIP expression was still high in bleomycin-treated MCF-7 cells. In addition, we observed that miR-15a expression was regulated by p53, and the effects of miR-15a on DNA damage was also mediated by p53. Furthermore, the results revealed that the cell apoptosis was mediated by miR-15a. Taken together, this study reveals that p53 negatively regulates NAIP expression by targeting miR-15a processing from primary into precursor miRNA in breast cancer.
Breast Cancer Center, Shandong Cancer Hospital Affiliated to Shandong University; Shandong Academy of Medical Sciences Jinan 250117, Shandong, P. R. China.
Li
L
Yang
Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University; Shandong Academy of Medical Sciences Jinan 250117, Shandong, P. R. China.
Wei
W
Zhao
Department of Gynecological Oncology, Shandong Cancer Hospital Affiliated to Shandong University; Shandong Academy of Medical Sciences Jinan 250117, Shandong, P. R. China.
Ping
P
Wei
Breast Cancer Center, Shandong Cancer Hospital Affiliated to Shandong University; Shandong Academy of Medical Sciences Jinan 250117, Shandong, P. R. China.
Wenshu
W
Zuo
Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University; Shandong Academy of Medical Sciences Jinan 250117, Shandong, P. R. China.
Shouhui
S
Zhu
Breast cancer; DNA damage; miR-15a; neuronal apoptosis inhibitory protein (NAIP); tumor suppressor p53