Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis
Haoyi Tang,
Shanghai Liu,
Xiangyu Yan,
Yusheng Jin,
Xiangyang He,
Hao Huang,
Lu Liu,
Wentao Hu,
Anqing Wu
Affiliations
Haoyi Tang
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Shanghai Liu
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Xiangyu Yan
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Yusheng Jin
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Xiangyang He
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Hao Huang
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Lu Liu
Suzhou Medical College, Soochow University, Suzhou 215123, China
Wentao Hu
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Anqing Wu
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
Lung cancer remains the leading cause of cancer-related deaths in both women and men, claiming millions of lives worldwide. Radiotherapy is an effective modality for treating early-stage lung cancer; however, it cannot completely eradicate certain tumor cells due to their radioresistance. Radioresistance is commonly observed in conventionally fractionated radiotherapy, which can lead to treatment failure, metastasis, cancer recurrence, and poor prognosis for cancer patients. Identifying the underlying molecular mechanisms of radioresistance in lung cancer can promote the development of effective radiosensitizers, thereby improving patients’ life expectancy and curability. In this study, we identified LNC EBLN3P as a regulator of lung cancer cell proliferation and radiosensitivity. The repression of LNC EBLN3P could increase ROS production and mitochondrial injury in NSCLC cells. In addition, knocking down LNC EBLN3P increased the binding of Nrf2 to Keap1, resulting in enhanced Nrf2 degradation, decreased translocation of Nrf2 to the nucleus, reduced expression of antioxidant protein HO-1, weakened cellular antioxidant capacity, and increased radiosensitivity of NSCLC cells. These findings suggest that targeting LNC EBLN3P could be a promising strategy for developing novel radiosensitizers in the context of conventional radiotherapy for NSCLC.
