Endogenous Bornavirus-Like Nucleoprotein 1 Regulates Cellular Processes and DNA Double-Strand Breaks in U-87 MG Glioblastoma Cells.

BACKGROUND

Glioblastoma (GBM) is a common brain cancer with a poor prognosis and a high recurrence rate. DNA damage repair plays a crucial role in GBM carcinogenesis and treatment resistance. Human endogenous bornavirus-like nucleoprotein 1 (EBLN1) regulates cellular processes and genetic stability. However, the biological role of EBLN1 in GBM remains unclear.

AIMS: This study aims to determine the role of EBLN1 in the regulation of cellular processes and DNA double-strand breaks (DSBs) in GBM and to investigate the underlying molecular mechanisms.

METHODS AND

RESULTS

U-87 MG GBM cells were infected with an shRNA-expressing lentivirus to knock down EBLN1. Then, cell proliferation and apoptosis were evaluated. The levels of DSBs, as well as the activities of two key DSB repair regulators-ataxia telangiectasia mutated (ATM) kinase and breast cancer Type 1 susceptibility protein (BRCA1)-were detected. Furthermore, after reactivating ATM, cellular processes and the levels of DSBs were re-detected to verify the mechanisms underlying EBLN1-mediated DNA repair regulation in GBM. EBLN1-silenced U-87 MG cells displayed a significant reduction in cell growth as early as the second day postinfection (p < 0.05) and a higher apoptosis ratio (p < 0.001). After EBLN1-silencing, U-87 MG cells exhibited a remarkable increase in the expression of γH2AX (p < 0.001) and significantly lower expression levels of ATM and BRCA1 (p < 0.001). After reactivation of ATM in EBLN1-silenced U-87 MG cells, DSB levels in the treated cells were significantly decreased (p < 0.001). Meanwhile, cell proliferation was significantly increased (p < 0.001), while apoptosis was markedly suppressed (p < 0.001).

CONCLUSION

This study uncovers a novel molecular mechanism that EBLN1 regulates cellular processes via modulating DNA double-strand break repair in glioblastoma cells, providing a new perspective for understanding the pathogenesis of GBM.