RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma
Abstract The therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer remains constrained and demonstrates substantial variability across different patients. Targeting the metabolism of tumors emerges an encouraging strategy to enhance the outcomes of tumor immunotherapy. We a...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-06-01
|
| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-025-00977-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850224064197558272 |
|---|---|
| author | Qingwu Du Rui Li Jian Wang Jingya Wang Yantao Jiang Qi Xu Dingzhi Huang Tingting Qin |
| author_facet | Qingwu Du Rui Li Jian Wang Jingya Wang Yantao Jiang Qi Xu Dingzhi Huang Tingting Qin |
| author_sort | Qingwu Du |
| collection | DOAJ |
| description | Abstract The therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer remains constrained and demonstrates substantial variability across different patients. Targeting the metabolism of tumors emerges an encouraging strategy to enhance the outcomes of tumor immunotherapy. We analyzed metabolic differences in lung cancer post-anti-PD-1 treatment using a single-cell RNA sequencing data (n = 15). Abnormal lipid metabolism is notable in patients with a non-major pathological response, and low RAN expression is linked to good immunotherapy response. RAN showed increased expression in lung adenocarcinoma (LUAD) versus normal lung tissues, correlating with worse prognosis, advanced staging, reduced immune cell activity, and greater sensitivity to common chemotherapeutic drugs. Knockdown of RAN caused G2/M phase arrest, inhibiting proliferation and clone formation in LUAD cells. RAN modifies lipid metabolism via nuclear p-AMPK output to aid tumor cells in resisting immunotherapy and reduces MHC-related molecule expression to evade CD8 + T cell detection. Combining Selinexor with immunotherapy might effectively counter immune tolerance and boost anti-tumor responses in LUAD. |
| format | Article |
| id | doaj-art-9e8d6e8fb2b94cc4998ea800453549b5 |
| institution | OA Journals |
| issn | 2397-768X |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj-art-9e8d6e8fb2b94cc4998ea800453549b52025-08-20T02:05:45ZengNature Portfolionpj Precision Oncology2397-768X2025-06-019111210.1038/s41698-025-00977-8RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinomaQingwu Du0Rui Li1Jian Wang2Jingya Wang3Yantao Jiang4Qi Xu5Dingzhi Huang6Tingting Qin7Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerAbstract The therapeutic effectiveness of immune checkpoint inhibitors (ICIs) in lung cancer remains constrained and demonstrates substantial variability across different patients. Targeting the metabolism of tumors emerges an encouraging strategy to enhance the outcomes of tumor immunotherapy. We analyzed metabolic differences in lung cancer post-anti-PD-1 treatment using a single-cell RNA sequencing data (n = 15). Abnormal lipid metabolism is notable in patients with a non-major pathological response, and low RAN expression is linked to good immunotherapy response. RAN showed increased expression in lung adenocarcinoma (LUAD) versus normal lung tissues, correlating with worse prognosis, advanced staging, reduced immune cell activity, and greater sensitivity to common chemotherapeutic drugs. Knockdown of RAN caused G2/M phase arrest, inhibiting proliferation and clone formation in LUAD cells. RAN modifies lipid metabolism via nuclear p-AMPK output to aid tumor cells in resisting immunotherapy and reduces MHC-related molecule expression to evade CD8 + T cell detection. Combining Selinexor with immunotherapy might effectively counter immune tolerance and boost anti-tumor responses in LUAD.https://doi.org/10.1038/s41698-025-00977-8 |
| spellingShingle | Qingwu Du Rui Li Jian Wang Jingya Wang Yantao Jiang Qi Xu Dingzhi Huang Tingting Qin RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma npj Precision Oncology |
| title | RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma |
| title_full | RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma |
| title_fullStr | RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma |
| title_full_unstemmed | RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma |
| title_short | RAN potentiates nuclear export of phosphorylated AMPK, reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma |
| title_sort | ran potentiates nuclear export of phosphorylated ampk reshaping lipid metabolism and impairing immune efficacy in lung adenocarcinoma |
| url | https://doi.org/10.1038/s41698-025-00977-8 |
| work_keys_str_mv | AT qingwudu ranpotentiatesnuclearexportofphosphorylatedampkreshapinglipidmetabolismandimpairingimmuneefficacyinlungadenocarcinoma AT ruili ranpotentiatesnuclearexportofphosphorylatedampkreshapinglipidmetabolismandimpairingimmuneefficacyinlungadenocarcinoma AT jianwang ranpotentiatesnuclearexportofphosphorylatedampkreshapinglipidmetabolismandimpairingimmuneefficacyinlungadenocarcinoma AT jingyawang ranpotentiatesnuclearexportofphosphorylatedampkreshapinglipidmetabolismandimpairingimmuneefficacyinlungadenocarcinoma AT yantaojiang ranpotentiatesnuclearexportofphosphorylatedampkreshapinglipidmetabolismandimpairingimmuneefficacyinlungadenocarcinoma AT qixu ranpotentiatesnuclearexportofphosphorylatedampkreshapinglipidmetabolismandimpairingimmuneefficacyinlungadenocarcinoma AT dingzhihuang ranpotentiatesnuclearexportofphosphorylatedampkreshapinglipidmetabolismandimpairingimmuneefficacyinlungadenocarcinoma AT tingtingqin ranpotentiatesnuclearexportofphosphorylatedampkreshapinglipidmetabolismandimpairingimmuneefficacyinlungadenocarcinoma |