The functions of the high mobility group box 1 (
HMGB1) in
tumor cells include replenishing telomeric
DNA and maintaining cell immortality. There is a negative correlation between human
telomerase reverse transcriptase (hTERT) and radiosensitivity in
tumor cells. Our aim was to elucidate the relationship among
HMGB1, telomere homeostasis and radiosensitivity in MCF-7 cells. In this study, we established stably transfected control (MCF-7-NC) and
HMGB1 knockdown (MCF-7-shHMGB1) cell lines. The expression of
HMGB1 mRNA and the relative telomere length were examined by real-time PCR. Radiosensitivity was detected by clonogenic assay. The
protein expressions were determined by western blot analysis. The
telomerase activity was detected by PCR-ELISA. Proliferation ability was examined by
CCK-8 assay. Cell cycle and apoptosis were examined by flow cytometry. DNA damage foci were detected by immunofluorescence.
ShRNA-mediated downregulation of
HMGB1 expression increased the radiosensitivity of MCF-7 cells, and reduced the accumulation of hTERT and
cyclin D1. Moreover, knockdown of
HMGB1 in MCF-7 cells inhibited
telomerase activity and cell proliferation, while increasing the extent of apoptosis. Downregulation of
HMGB1 modulated telomere homeostasis by changing the level of
telomere-binding proteins, such as TPP1 (PTOP), TRF1 and TRF2. This downregulation also inhibited the ATM and ATR signaling pathways. The current data demonstrate that knockdown of
HMGB1 breaks telomere homeostasis, enhances radiosensitivity, and suppresses the repair of DNA damage in human
breast cancer cells. These results suggested that
HMGB1 might be a potential
radiotherapy target in human
breast cancer.