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

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.

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.

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).

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.