Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
The stress response molecule nuclear protein‑1 (NUPR1) is essential for the growth of multiple types of human malignant tumor cells. However, the significance of NUPR1 in lung cancer is still not entirely elucidated. Therefore, this study is aimed to explore the function and underlying mechanisms of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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De Gruyter
2023-10-01
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| Series: | Open Medicine |
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| Online Access: | https://doi.org/10.1515/med-2023-0796 |
| _version_ | 1797653385383510016 |
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| author | Wang Lihuai Wen Jing Sun Yinhui Yang Xiao Ma Yi Tian Xuefei |
| author_facet | Wang Lihuai Wen Jing Sun Yinhui Yang Xiao Ma Yi Tian Xuefei |
| author_sort | Wang Lihuai |
| collection | DOAJ |
| description | The stress response molecule nuclear protein‑1 (NUPR1) is essential for the growth of multiple types of human malignant tumor cells. However, the significance of NUPR1 in lung cancer is still not entirely elucidated. Therefore, this study is aimed to explore the function and underlying mechanisms of NUPR1 in lung cancer. NUPR1 mRNA and protein levels in lung cancer cell lines (A549 or H1299 cells) were silenced through siRNA transfection and western blot observed its successful infection efficiency. Then, using tube formation and wound healing experiments, the effects of si-NUPR1 on angiogenesis and migration of human umbilical vein endothelial cells (HUVEC) were examined, respectively, which indicated inhibitory effects on the angiogenesis and migration of HUVEC. Vascular endothelial growth factor A (VEGFA), a vital molecule in angiogenesis, was detected by PCR and western blot assays, manifesting NUPR1 knockdown represses VEGFA expression. Furthermore, the knockdown of NUPR1 may reduce angiogenesis by lowering VEGFA expression through inositol-requiring enzyme 1 (IRE1)/X box binding protein 1 (XBP1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 A (eIF2α)/recombinant activating transcription factor 4 (ATF4) signaling pathways in A549 or H1299 cells. In conclusion, these findings demonstrated that NUPR1 knockdown inhibits angiogenesis in A549 and H1299 cells through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways, indicating that NUPR1 could represent a novel lung cancer therapeutic target. |
| first_indexed | 2024-03-11T16:43:53Z |
| format | Article |
| id | doaj.art-fe2e05a2021c418fa447beb12ac8cc79 |
| institution | Directory Open Access Journal |
| issn | 2391-5463 |
| language | English |
| last_indexed | 2024-03-11T16:43:53Z |
| publishDate | 2023-10-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Open Medicine |
| spelling | doaj.art-fe2e05a2021c418fa447beb12ac8cc792023-10-23T07:50:42ZengDe GruyterOpen Medicine2391-54632023-10-0118113678010.1515/med-2023-0796Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathwaysWang Lihuai0Wen Jing1Sun Yinhui2Yang Xiao3Ma Yi4Tian Xuefei5School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, ChinaDepartment of Oncology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410000, ChinaSchool of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, 410208, ChinaDepartment of Oncology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410000, ChinaDepartment of Oncology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410000, ChinaCollege of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, No. 300 Xueshi Road, Yuelu District, Changsha, Hunan, 410208, ChinaThe stress response molecule nuclear protein‑1 (NUPR1) is essential for the growth of multiple types of human malignant tumor cells. However, the significance of NUPR1 in lung cancer is still not entirely elucidated. Therefore, this study is aimed to explore the function and underlying mechanisms of NUPR1 in lung cancer. NUPR1 mRNA and protein levels in lung cancer cell lines (A549 or H1299 cells) were silenced through siRNA transfection and western blot observed its successful infection efficiency. Then, using tube formation and wound healing experiments, the effects of si-NUPR1 on angiogenesis and migration of human umbilical vein endothelial cells (HUVEC) were examined, respectively, which indicated inhibitory effects on the angiogenesis and migration of HUVEC. Vascular endothelial growth factor A (VEGFA), a vital molecule in angiogenesis, was detected by PCR and western blot assays, manifesting NUPR1 knockdown represses VEGFA expression. Furthermore, the knockdown of NUPR1 may reduce angiogenesis by lowering VEGFA expression through inositol-requiring enzyme 1 (IRE1)/X box binding protein 1 (XBP1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2 A (eIF2α)/recombinant activating transcription factor 4 (ATF4) signaling pathways in A549 or H1299 cells. In conclusion, these findings demonstrated that NUPR1 knockdown inhibits angiogenesis in A549 and H1299 cells through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways, indicating that NUPR1 could represent a novel lung cancer therapeutic target.https://doi.org/10.1515/med-2023-0796nupr1lung cancerangiogenesissignaling pathways |
| spellingShingle | Wang Lihuai Wen Jing Sun Yinhui Yang Xiao Ma Yi Tian Xuefei Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways Open Medicine nupr1 lung cancer angiogenesis signaling pathways |
| title | Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways |
| title_full | Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways |
| title_fullStr | Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways |
| title_full_unstemmed | Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways |
| title_short | Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways |
| title_sort | knockdown of nupr1 inhibits angiogenesis in lung cancer through ire1 xbp1 and perk eif2α atf4 signaling pathways |
| topic | nupr1 lung cancer angiogenesis signaling pathways |
| url | https://doi.org/10.1515/med-2023-0796 |
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