METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
Overexpression of methyltransferase-like 3 (METTL3) is significantly correlated with the malignancy of lung cancer (LC). In the present study, we demonstrated that METTL3 had higher levels in LC tissues relative to normal tissues. METTL3 showed superior sensitivity and specificity for diagnosis and...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
De Gruyter
2024-01-01
|
| Series: | Open Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1515/med-2023-0882 |
| _version_ | 1797354378863050752 |
|---|---|
| author | Zhang Peng Wang Su Chen Yuanyuan Yang Qingbo Zhou Jian Zang Wangfu |
| author_facet | Zhang Peng Wang Su Chen Yuanyuan Yang Qingbo Zhou Jian Zang Wangfu |
| author_sort | Zhang Peng |
| collection | DOAJ |
| description | Overexpression of methyltransferase-like 3 (METTL3) is significantly correlated with the malignancy of lung cancer (LC). In the present study, we demonstrated that METTL3 had higher levels in LC tissues relative to normal tissues. METTL3 showed superior sensitivity and specificity for diagnosis and identification of LC functions. In addition, silencing METTL3 resulted in enhanced ferroptosis sensitivity, whereas overexpression of METTL3 exhibited the opposite effect. Inhibition of METTL3 impeded LC growth in cell-derived xenografts. Further exploratory studies found that METTL3 stimulated the low expression of transferrin receptor (TFRC), which was critical for ferroptosis sensitization in LC cells induced by silenced METTL3, as silencing of TFRC caused a decrease in negative regulators of ferroptosis (FTH1 and FTL) in METTL3 knockdown A549 and PC9 cells. Finally, we confirmed that METTL3 attenuation effectively maintained the stability of TFRC mRNA. In conclusion, we reported a novel mechanism of METTL3 desensitization to ferroptosis via regulating TFRC, and an appropriate reduction of METTL3 might sensitize cancer cells to ferroptosis-based therapy. |
| first_indexed | 2024-03-08T13:49:36Z |
| format | Article |
| id | doaj.art-bc522a8157114d53a2b67ff1a6acf71e |
| institution | Directory Open Access Journal |
| issn | 2391-5463 |
| language | English |
| last_indexed | 2024-03-08T13:49:36Z |
| publishDate | 2024-01-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Medicine |
| spelling | doaj.art-bc522a8157114d53a2b67ff1a6acf71e2024-01-16T07:18:43ZengDe GruyterOpen Medicine2391-54632024-01-011912094910.1515/med-2023-0882METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRCZhang Peng0Wang Su1Chen Yuanyuan2Yang Qingbo3Zhou Jian4Zang Wangfu5Department of Cardio-Thoracic Surgery, Shanghai Tenth People’s Hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai200072, ChinaDepartment of Cardio-Thoracic Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai200072, ChinaDepartment of Cardio-Thoracic Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai200072, ChinaDepartment of Cardio-Thoracic Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai200072, ChinaDepartment of Cardio-Thoracic Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai200072, ChinaDepartment of Cardio-Thoracic Surgery, Shanghai Tenth People’s Hospital, School of Clinical Medicine of Nanjing Medical University, No. 301 Yanchang Middle Road, Jing'an DistrictShanghai200072, ChinaOverexpression of methyltransferase-like 3 (METTL3) is significantly correlated with the malignancy of lung cancer (LC). In the present study, we demonstrated that METTL3 had higher levels in LC tissues relative to normal tissues. METTL3 showed superior sensitivity and specificity for diagnosis and identification of LC functions. In addition, silencing METTL3 resulted in enhanced ferroptosis sensitivity, whereas overexpression of METTL3 exhibited the opposite effect. Inhibition of METTL3 impeded LC growth in cell-derived xenografts. Further exploratory studies found that METTL3 stimulated the low expression of transferrin receptor (TFRC), which was critical for ferroptosis sensitization in LC cells induced by silenced METTL3, as silencing of TFRC caused a decrease in negative regulators of ferroptosis (FTH1 and FTL) in METTL3 knockdown A549 and PC9 cells. Finally, we confirmed that METTL3 attenuation effectively maintained the stability of TFRC mRNA. In conclusion, we reported a novel mechanism of METTL3 desensitization to ferroptosis via regulating TFRC, and an appropriate reduction of METTL3 might sensitize cancer cells to ferroptosis-based therapy.https://doi.org/10.1515/med-2023-0882lung cancerferroptosismettl3tfrc |
| spellingShingle | Zhang Peng Wang Su Chen Yuanyuan Yang Qingbo Zhou Jian Zang Wangfu METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC Open Medicine lung cancer ferroptosis mettl3 tfrc |
| title | METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC |
| title_full | METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC |
| title_fullStr | METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC |
| title_full_unstemmed | METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC |
| title_short | METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC |
| title_sort | mettl3 attenuates ferroptosis sensitivity in lung cancer via modulating tfrc |
| topic | lung cancer ferroptosis mettl3 tfrc |
| url | https://doi.org/10.1515/med-2023-0882 |
| work_keys_str_mv | AT zhangpeng mettl3attenuatesferroptosissensitivityinlungcancerviamodulatingtfrc AT wangsu mettl3attenuatesferroptosissensitivityinlungcancerviamodulatingtfrc AT chenyuanyuan mettl3attenuatesferroptosissensitivityinlungcancerviamodulatingtfrc AT yangqingbo mettl3attenuatesferroptosissensitivityinlungcancerviamodulatingtfrc AT zhoujian mettl3attenuatesferroptosissensitivityinlungcancerviamodulatingtfrc AT zangwangfu mettl3attenuatesferroptosissensitivityinlungcancerviamodulatingtfrc |