LncRNA-EME1 enhances BRCA1 recruitment and alters repair of DNA damage in cervical cancer radioresistance.

BACKGROUND: Cervical cancer is a significant cause of mortality in women globally, and radioresistance limits the effectiveness of standard radiotherapy treatment. Exploring the molecular mechanisms that contribute to radioresistance is vital for improving therapies. This study focuses on the role of lncRNA in influencing the radioresistance of cervical cancer. METHODS: We identified lncRNA-EME1 as a candidate regulator of cervical cancer radioresistance through transcriptomic sequencing and RT-qPCR. Its function was explored by silencing or overexpressing lncRNA-EME1, followed by proliferation (MTT), clonogenic survival, apoptosis, and ROS assays. Effects on BRCA1 expression and DNA damage response were examined by WB, γ-H2AX focus analysis, and the I-SceI-mediated homologous recombination assay. Mechanistic insights were obtained using RNA pull-down and RIP assays. Finally, a xenograft model with subsequent TUNEL and immunohistochemical analyses was used to validate the role of lncRNA-EME1 in regulating BRCA1 and mediating radioresistance in vivo. RESULTS: Our findings indicate that lncRNA-EME1 is overexpressed in radioresistant cervical cancer cells. Silencing lncRNA-EME1 enhances radiosensitivity in HeLa-IR and SiHa-IR cells, suppresses malignant phenotypes, and increases apoptosis and ROS levels. This effects corresponds with reduced BRCA1 expression and alterations in DNA damage repair markers, highlighting its role in the radiation response. The positive association between lncRNA-EME1 and BRCA1 further supports its involvement in DNA damage repair, thereby regulating cervical cancer cells' sensitivity to radiation therapy. In vivo xenograft experiments further confirmed that lncRNA-EME1 promotes BRCA1 expression and contributes to cervical cancer radioresistance. CONCLUSION: This study sheds light on the role of lncRNA-EME1 in regulating BRCA1 activity and contributing to cervical cancer radioresistance. Our data reveals that decreasing lncRNA-EME1 expression could potentially boost radiosensitivity in cervical cancer cells.