lncRNA GAS5 Sensitizes Breast Cancer Cells to Ionizing Radiation by Inhibiting DNA Repair.
Yan MaLei YuWenxing YanLing QiuJianqiu ZhangXiaojing JiaPublished in: BioMed research international (2022)
Radioresistance of breast cancer is a major reason for therapeutic failure and limits further increases in the dose of radiation due to severe adverse effects. Recently, long noncoding RNAs (lncRNAs) have been shown to regulate cancer proliferation, chemoresistance, and radioresistance. Among these lncRNAs, lncRNA GAS5 expression was shown to be downregulated in breast cancer and related to trastuzumab resistance. However, its role in the radiation response is unclear. In this study, we demonstrated that lncRNA GAS5 expression was reduced in irradiated cells and that overexpression of GAS5 reduced cell viability and promoted cell apoptosis after irradiation. Moreover, overexpression of GAS5 resulted in increased G2/M arrest and unrepaired DNA damage, indicating a radiosensitizing role of GAS5 in breast cancer cells. Finally, we found that a GAS5-interacting miRNA, miR-21, reversed the radiosensitizing effects of GAS5 by inhibiting the apoptotic pathway. In conclusion, we found that lncRNA GAS5 sensitized breast cancer cells to ionizing radiation by inhibiting DNA repair and suppressing miR-21, identifying novel targets for breast cancer radiosensitization.
Keyphrases
- dna repair
- dna damage
- room temperature
- breast cancer cells
- long non coding rna
- cell proliferation
- signaling pathway
- carbon dioxide
- long noncoding rna
- poor prognosis
- dna damage response
- induced apoptosis
- oxidative stress
- radiation therapy
- cell cycle
- squamous cell carcinoma
- young adults
- endoplasmic reticulum stress
- radiation induced
- transcription factor
- cell cycle arrest
- drug induced
- anti inflammatory