PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways
Abstract Background PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated. Methods ShRNA knockdown and overexpression of P...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4391-9 |
| _version_ | 1819291212634390528 |
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| author | Dong-Dong Wu Ying-Ran Gao Tao Li Da-Yong Wang Dan Lu Shi-Yu Liu Ya Hong Hui-Bin Ning Jun-Ping Liu Jia Shang Jun-Feng Shi Jian-She Wei Xin-Ying Ji |
| author_facet | Dong-Dong Wu Ying-Ran Gao Tao Li Da-Yong Wang Dan Lu Shi-Yu Liu Ya Hong Hui-Bin Ning Jun-Ping Liu Jia Shang Jun-Feng Shi Jian-She Wei Xin-Ying Ji |
| author_sort | Dong-Dong Wu |
| collection | DOAJ |
| description | Abstract Background PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated. Methods ShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo. Results PCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis. Conclusions PCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma. |
| first_indexed | 2024-12-24T03:35:03Z |
| format | Article |
| id | doaj.art-dcd2b6903c4f4f28aa2c15e07c748282 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-24T03:35:03Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-dcd2b6903c4f4f28aa2c15e07c7482822022-12-21T17:17:06ZengBMCBMC Cancer1471-24072018-05-0118111510.1186/s12885-018-4391-9PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathwaysDong-Dong Wu0Ying-Ran Gao1Tao Li2Da-Yong Wang3Dan Lu4Shi-Yu Liu5Ya Hong6Hui-Bin Ning7Jun-Ping Liu8Jia Shang9Jun-Feng Shi10Jian-She Wei11Xin-Ying Ji12School of Basic Medical Sciences, Henan University College of MedicineSchool of Basic Medical Sciences, Henan University College of MedicineSchool of Basic Medical Sciences, Henan University College of MedicineSchool of Basic Medical Sciences, Henan University College of MedicineSchool of Basic Medical Sciences, Henan University College of MedicineSchool of Basic Medical Sciences, Henan University College of MedicineSchool of Basic Medical Sciences, Henan University College of MedicineHenan Provincial People’s Hospital Affiliated to Henan UniversityHenan Provincial People’s Hospital Affiliated to Henan UniversityHenan Provincial People’s Hospital Affiliated to Henan UniversityNanyang Nanshi Hospital Affiliated to Henan UniversityBrain Research Laboratory, College of Life Sciences, Henan UniversitySchool of Basic Medical Sciences, Henan University College of MedicineAbstract Background PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated. Methods ShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo. Results PCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis. Conclusions PCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma.http://link.springer.com/article/10.1186/s12885-018-4391-9PEST-containing nuclear proteinNeuroblastomaAngiogenesisApoptosisSignaling pathway |
| spellingShingle | Dong-Dong Wu Ying-Ran Gao Tao Li Da-Yong Wang Dan Lu Shi-Yu Liu Ya Hong Hui-Bin Ning Jun-Ping Liu Jia Shang Jun-Feng Shi Jian-She Wei Xin-Ying Ji PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways BMC Cancer PEST-containing nuclear protein Neuroblastoma Angiogenesis Apoptosis Signaling pathway |
| title | PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways |
| title_full | PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways |
| title_fullStr | PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways |
| title_full_unstemmed | PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways |
| title_short | PEST-containing nuclear protein mediates the proliferation, migration, and invasion of human neuroblastoma cells through MAPK and PI3K/AKT/mTOR signaling pathways |
| title_sort | pest containing nuclear protein mediates the proliferation migration and invasion of human neuroblastoma cells through mapk and pi3k akt mtor signaling pathways |
| topic | PEST-containing nuclear protein Neuroblastoma Angiogenesis Apoptosis Signaling pathway |
| url | http://link.springer.com/article/10.1186/s12885-018-4391-9 |
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