Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis
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. Radioresis...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-7737/12/9/1208 |
| _version_ | 1797581183921422336 |
|---|---|
| author | Haoyi Tang Shanghai Liu Xiangyu Yan Yusheng Jin Xiangyang He Hao Huang Lu Liu Wentao Hu Anqing Wu |
| author_facet | Haoyi Tang Shanghai Liu Xiangyu Yan Yusheng Jin Xiangyang He Hao Huang Lu Liu Wentao Hu Anqing Wu |
| author_sort | Haoyi Tang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T23:01:42Z |
| format | Article |
| id | doaj.art-b208e6605b6b4e0380b5df0c26ccc153 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T23:01:42Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-b208e6605b6b4e0380b5df0c26ccc1532023-11-19T09:38:33ZengMDPI AGBiology2079-77372023-09-01129120810.3390/biology12091208Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 AxisHaoyi Tang0Shanghai Liu1Xiangyu Yan2Yusheng Jin3Xiangyang He4Hao Huang5Lu Liu6Wentao Hu7Anqing Wu8State 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaSuzhou Medical College, Soochow University, Suzhou 215123, ChinaState 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, ChinaState 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, ChinaLung 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.https://www.mdpi.com/2079-7737/12/9/1208lung cancerlong non-coding RNAradiotherapyradiosensitivitymitochondrial damage |
| spellingShingle | Haoyi Tang Shanghai Liu Xiangyu Yan Yusheng Jin Xiangyang He Hao Huang Lu Liu Wentao Hu Anqing Wu Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis Biology lung cancer long non-coding RNA radiotherapy radiosensitivity mitochondrial damage |
| title | Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis |
| title_full | Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis |
| title_fullStr | Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis |
| title_full_unstemmed | Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis |
| title_short | Inhibition of LNC EBLN3P Enhances Radiation-Induced Mitochondrial Damage in Lung Cancer Cells by Targeting the Keap1/Nrf2/HO-1 Axis |
| title_sort | inhibition of lnc ebln3p enhances radiation induced mitochondrial damage in lung cancer cells by targeting the keap1 nrf2 ho 1 axis |
| topic | lung cancer long non-coding RNA radiotherapy radiosensitivity mitochondrial damage |
| url | https://www.mdpi.com/2079-7737/12/9/1208 |
| work_keys_str_mv | AT haoyitang inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis AT shanghailiu inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis AT xiangyuyan inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis AT yushengjin inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis AT xiangyanghe inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis AT haohuang inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis AT luliu inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis AT wentaohu inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis AT anqingwu inhibitionoflncebln3penhancesradiationinducedmitochondrialdamageinlungcancercellsbytargetingthekeap1nrf2ho1axis |