Cargando…
RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer
BACKGROUND: Bladder cancer (BCa) represents one of the most common malignant cancers with high incidence and mortality rates globally. Dysregulation of gene expression has been shown to play critical roles in cancer progression. RAC3 is up-regulated to play an oncogenic role in several cancers, howe...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488983/ https://www.ncbi.nlm.nih.gov/pubmed/33062641 http://dx.doi.org/10.3389/fmolb.2020.00218 |
_version_ | 1783581797622218752 |
---|---|
author | Cheng, Chuanyu Song, Dongkui Wu, Yudong Liu, Bingqian |
author_facet | Cheng, Chuanyu Song, Dongkui Wu, Yudong Liu, Bingqian |
author_sort | Cheng, Chuanyu |
collection | PubMed |
description | BACKGROUND: Bladder cancer (BCa) represents one of the most common malignant cancers with high incidence and mortality rates globally. Dysregulation of gene expression has been shown to play critical roles in cancer progression. RAC3 is up-regulated to play an oncogenic role in several cancers, however, the underlying mechanism of RAC3 in BCa is yet to be elucidated. Therefore, this study aimed to investigate the function and mechanism of RAC3 in BCa. METHODS: Bioinformatics analysis was employed to demonstrate the expression of RAC3 and PYCR1 in BCa tissues, as well as, its correlation with the overall survival rate of BCa patients. RT-qPCR was performed to detect and quantify the mRNA levels of RAC3 and PYCR1 in BCa cells and immortalized human bladder epithelial cells. MTT, colony formation and Transwell assays were employed to determine cell proliferation, migration, and invasion. Western blotting was performed to detect and quantity proteins expressed. RESULTS: Bioinformatics analysis showed that RAC3 was up-regulated in BCa tissues when compared to normal tissues. Patients with up-regulated RAC3 expression had lower overall survival than patients with down-regulated RAC3 expression. The mRNA level of RAC3 was higher in BCa cells than in immortalized human bladder epithelial cell. RAC3 promoted cell proliferation, migration, and invasion by activating Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling. Notably, RAC3 up-regulated PYCR1, which is positively correlated with RAC3, and thus played an oncogenic role in BCa cells. Moreover, we demonstrated that RAC3 overexpression activated JAK/STAT signaling via PYCR1 axis. CONCLUSION: RAC3 promoted cell proliferation, migration, and invasion. This is likely due to its role in activating JAK/STAT signaling, which was mediated by PYCR1. This study provides a novel biomarker and target for diagnostic or therapeutic intervention for BCa. |
format | Online Article Text |
id | pubmed-7488983 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74889832020-10-14 RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer Cheng, Chuanyu Song, Dongkui Wu, Yudong Liu, Bingqian Front Mol Biosci Molecular Biosciences BACKGROUND: Bladder cancer (BCa) represents one of the most common malignant cancers with high incidence and mortality rates globally. Dysregulation of gene expression has been shown to play critical roles in cancer progression. RAC3 is up-regulated to play an oncogenic role in several cancers, however, the underlying mechanism of RAC3 in BCa is yet to be elucidated. Therefore, this study aimed to investigate the function and mechanism of RAC3 in BCa. METHODS: Bioinformatics analysis was employed to demonstrate the expression of RAC3 and PYCR1 in BCa tissues, as well as, its correlation with the overall survival rate of BCa patients. RT-qPCR was performed to detect and quantify the mRNA levels of RAC3 and PYCR1 in BCa cells and immortalized human bladder epithelial cells. MTT, colony formation and Transwell assays were employed to determine cell proliferation, migration, and invasion. Western blotting was performed to detect and quantity proteins expressed. RESULTS: Bioinformatics analysis showed that RAC3 was up-regulated in BCa tissues when compared to normal tissues. Patients with up-regulated RAC3 expression had lower overall survival than patients with down-regulated RAC3 expression. The mRNA level of RAC3 was higher in BCa cells than in immortalized human bladder epithelial cell. RAC3 promoted cell proliferation, migration, and invasion by activating Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) signaling. Notably, RAC3 up-regulated PYCR1, which is positively correlated with RAC3, and thus played an oncogenic role in BCa cells. Moreover, we demonstrated that RAC3 overexpression activated JAK/STAT signaling via PYCR1 axis. CONCLUSION: RAC3 promoted cell proliferation, migration, and invasion. This is likely due to its role in activating JAK/STAT signaling, which was mediated by PYCR1. This study provides a novel biomarker and target for diagnostic or therapeutic intervention for BCa. Frontiers Media S.A. 2020-08-31 /pmc/articles/PMC7488983/ /pubmed/33062641 http://dx.doi.org/10.3389/fmolb.2020.00218 Text en Copyright © 2020 Cheng, Song, Wu and Liu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Cheng, Chuanyu Song, Dongkui Wu, Yudong Liu, Bingqian RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer |
title | RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer |
title_full | RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer |
title_fullStr | RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer |
title_full_unstemmed | RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer |
title_short | RAC3 Promotes Proliferation, Migration and Invasion via PYCR1/JAK/STAT Signaling in Bladder Cancer |
title_sort | rac3 promotes proliferation, migration and invasion via pycr1/jak/stat signaling in bladder cancer |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488983/ https://www.ncbi.nlm.nih.gov/pubmed/33062641 http://dx.doi.org/10.3389/fmolb.2020.00218 |
work_keys_str_mv | AT chengchuanyu rac3promotesproliferationmigrationandinvasionviapycr1jakstatsignalinginbladdercancer AT songdongkui rac3promotesproliferationmigrationandinvasionviapycr1jakstatsignalinginbladdercancer AT wuyudong rac3promotesproliferationmigrationandinvasionviapycr1jakstatsignalinginbladdercancer AT liubingqian rac3promotesproliferationmigrationandinvasionviapycr1jakstatsignalinginbladdercancer |