Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion
Non-small cell lung cancer (NSCLC) is the most common type of lung tumor; however, we lack effective early detection indicators and therapeutic targets. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is vital to initiate protein synthesis, acting as a scaffolding protein for the eukaryo...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2024-02-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1346383/full |
| _version_ | 1797319419771224064 |
|---|---|
| author | Ziyang He Fangyi Li Xinyi Zhang Dacheng Gao Zhiwen Zhang Rui Xu Xingguo Cao Qiyuan Shan Zhen Ren Yali Liu Zengguang Xu |
| author_facet | Ziyang He Fangyi Li Xinyi Zhang Dacheng Gao Zhiwen Zhang Rui Xu Xingguo Cao Qiyuan Shan Zhen Ren Yali Liu Zengguang Xu |
| author_sort | Ziyang He |
| collection | DOAJ |
| description | Non-small cell lung cancer (NSCLC) is the most common type of lung tumor; however, we lack effective early detection indicators and therapeutic targets. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is vital to initiate protein synthesis, acting as a scaffolding protein for the eukaryotic protein translation initiation factor complex, EIF4F, which regulates protein synthesis together with EIF4A, EIF4E, and other translation initiation factors. However, EIF4G1’s function in NSCLC cancer is unclear. Herein, transcriptome sequencing showed that knockdown of EIF4G1 in H1299 NSCLC cells upregulated the expression of various inflammation-related factors. Inflammatory cytokines were also significantly overexpressed in NSCLC tumor tissues, among which CXCL8 (encoding C-X-C motif chemokine ligand 8) showed the most significant changes in both in the transcriptome sequencing data and tumor tissues. We revealed that EIF4G1 regulates the protein level of TNF receptor superfamily member 10a (TNFRSF10A) resulting in activation of the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) pathways, which induces CXCL8 secretion, leading to targeted chemotaxis of immune cells. We verified that H1299 cells with EIF4G1 knockdown showed increased chemotaxis compared with the control group and promoted increased chemotaxis of macrophages. These data suggested that EIF4G1 is an important molecule in the inflammatory response of cancer tissues in NSCLC. |
| first_indexed | 2024-03-08T04:06:38Z |
| format | Article |
| id | doaj.art-73a4bdd9d0d44d87a62aaaa4e3376fe3 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T04:06:38Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-73a4bdd9d0d44d87a62aaaa4e3376fe32024-02-09T04:53:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-02-011510.3389/fphar.2024.13463831346383Knockdown of EIF4G1 in NSCLC induces CXCL8 secretionZiyang He0Fangyi Li1Xinyi Zhang2Dacheng Gao3Zhiwen Zhang4Rui Xu5Xingguo Cao6Qiyuan Shan7Zhen Ren8Yali Liu9Zengguang Xu10Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaShanghai East Hospital, Postgraduate Training Base of Jinzhou Medical University, Shanghai, ChinaShanghai East Hospital, Postgraduate Training Base of Jinzhou Medical University, Shanghai, ChinaResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaResearch Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaNon-small cell lung cancer (NSCLC) is the most common type of lung tumor; however, we lack effective early detection indicators and therapeutic targets. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is vital to initiate protein synthesis, acting as a scaffolding protein for the eukaryotic protein translation initiation factor complex, EIF4F, which regulates protein synthesis together with EIF4A, EIF4E, and other translation initiation factors. However, EIF4G1’s function in NSCLC cancer is unclear. Herein, transcriptome sequencing showed that knockdown of EIF4G1 in H1299 NSCLC cells upregulated the expression of various inflammation-related factors. Inflammatory cytokines were also significantly overexpressed in NSCLC tumor tissues, among which CXCL8 (encoding C-X-C motif chemokine ligand 8) showed the most significant changes in both in the transcriptome sequencing data and tumor tissues. We revealed that EIF4G1 regulates the protein level of TNF receptor superfamily member 10a (TNFRSF10A) resulting in activation of the mitogen activated protein kinase (MAPK) and nuclear factor kappa B (NFκB) pathways, which induces CXCL8 secretion, leading to targeted chemotaxis of immune cells. We verified that H1299 cells with EIF4G1 knockdown showed increased chemotaxis compared with the control group and promoted increased chemotaxis of macrophages. These data suggested that EIF4G1 is an important molecule in the inflammatory response of cancer tissues in NSCLC.https://www.frontiersin.org/articles/10.3389/fphar.2024.1346383/fullNSCLCEIF4G1CXCL8IL8chemotaxisMAPK |
| spellingShingle | Ziyang He Fangyi Li Xinyi Zhang Dacheng Gao Zhiwen Zhang Rui Xu Xingguo Cao Qiyuan Shan Zhen Ren Yali Liu Zengguang Xu Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion Frontiers in Pharmacology NSCLC EIF4G1 CXCL8 IL8 chemotaxis MAPK |
| title | Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion |
| title_full | Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion |
| title_fullStr | Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion |
| title_full_unstemmed | Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion |
| title_short | Knockdown of EIF4G1 in NSCLC induces CXCL8 secretion |
| title_sort | knockdown of eif4g1 in nsclc induces cxcl8 secretion |
| topic | NSCLC EIF4G1 CXCL8 IL8 chemotaxis MAPK |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1346383/full |
| work_keys_str_mv | AT ziyanghe knockdownofeif4g1innsclcinducescxcl8secretion AT fangyili knockdownofeif4g1innsclcinducescxcl8secretion AT xinyizhang knockdownofeif4g1innsclcinducescxcl8secretion AT dachenggao knockdownofeif4g1innsclcinducescxcl8secretion AT zhiwenzhang knockdownofeif4g1innsclcinducescxcl8secretion AT ruixu knockdownofeif4g1innsclcinducescxcl8secretion AT xingguocao knockdownofeif4g1innsclcinducescxcl8secretion AT qiyuanshan knockdownofeif4g1innsclcinducescxcl8secretion AT zhenren knockdownofeif4g1innsclcinducescxcl8secretion AT yaliliu knockdownofeif4g1innsclcinducescxcl8secretion AT zengguangxu knockdownofeif4g1innsclcinducescxcl8secretion |