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RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer

Background: Recently, the molecular classification of gastric cancer (GC) promotes the advances of GC patients' precision therapy and prognosis prediction. According to the Asian Cancer Research Group (ACRG), GC is classified as microsatellite instable (MSI) subtype GC, microsatellite stable/ep...

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Autores principales: Ma, Zhijie, Sun, Qi, Zhang, Chengfei, Zheng, Qian, Liu, Yixuan, Xu, Haojun, He, Yiting, Yao, Chengyun, Chen, Jinfei, Xia, Hongping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535698/
https://www.ncbi.nlm.nih.gov/pubmed/37781036
http://dx.doi.org/10.7150/ijbs.81972
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author Ma, Zhijie
Sun, Qi
Zhang, Chengfei
Zheng, Qian
Liu, Yixuan
Xu, Haojun
He, Yiting
Yao, Chengyun
Chen, Jinfei
Xia, Hongping
author_facet Ma, Zhijie
Sun, Qi
Zhang, Chengfei
Zheng, Qian
Liu, Yixuan
Xu, Haojun
He, Yiting
Yao, Chengyun
Chen, Jinfei
Xia, Hongping
author_sort Ma, Zhijie
collection PubMed
description Background: Recently, the molecular classification of gastric cancer (GC) promotes the advances of GC patients' precision therapy and prognosis prediction. According to the Asian Cancer Research Group (ACRG), GC is classified as microsatellite instable (MSI) subtype GC, microsatellite stable/epithelial-to-mesenchymal transition (MSS/EMT) subtype GC, MSS/TP53- subtype GC, and MSS/TP53+ subtype GC. Due to the easy metastasis of EMT-subtype GC, it has the worst prognosis, the highest recurrence rate, and the tendency to occur at a younger age. Therefore, it is curious and crucial for us to understand the molecular basis of EMT-subtype GC. Methods: The expression of RHOJ was detected by quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) in GC cells and tissues. Western blotting and immunofluorescence (IF) were conducted to examine the effects of RHOJ on the EMT markers' expression of GC cells. The GC cells' migration and invasion were investigated by transwell assay. The tumor growth and metastasis were demonstrated correspondingly in different xenograft models. Results: Firstly, it was noticed that RHOJ was significantly upregulated in EMT-subtype GC and RHOJ has close relationships with the EMT process of GC, based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Next, transwell assay and tail vein metastasis models were conducted to verify that RHOJ mediates the EMT to regulate the invasion and metastasis of GC in vitro and in vivo. In addition, weakened tumor angiogenesis was observed after RHOJ knockdown by the angiogenesis assay of HUVEC. RNA-seq and further study unveiled that RHOJ aggravates the malignant progression of GC by inducing EMT through IL-6/STAT3 to promote invasion and metastasis. Finally, blocking the IL-6/STAT3 signaling overcame RHOJ-mediated GC cells' growth and migration. Conclusions: These results indicate that the upregulation of RHOJ contributes to EMT-subtype GC invasion and metastasis via IL-6/STAT3 signaling, and RHOJ is expected to become a promising biomarker and therapeutic target for EMT-subtype GC patients.
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spelling pubmed-105356982023-09-29 RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer Ma, Zhijie Sun, Qi Zhang, Chengfei Zheng, Qian Liu, Yixuan Xu, Haojun He, Yiting Yao, Chengyun Chen, Jinfei Xia, Hongping Int J Biol Sci Research Paper Background: Recently, the molecular classification of gastric cancer (GC) promotes the advances of GC patients' precision therapy and prognosis prediction. According to the Asian Cancer Research Group (ACRG), GC is classified as microsatellite instable (MSI) subtype GC, microsatellite stable/epithelial-to-mesenchymal transition (MSS/EMT) subtype GC, MSS/TP53- subtype GC, and MSS/TP53+ subtype GC. Due to the easy metastasis of EMT-subtype GC, it has the worst prognosis, the highest recurrence rate, and the tendency to occur at a younger age. Therefore, it is curious and crucial for us to understand the molecular basis of EMT-subtype GC. Methods: The expression of RHOJ was detected by quantitative real-time PCR (qPCR) and immunohistochemistry (IHC) in GC cells and tissues. Western blotting and immunofluorescence (IF) were conducted to examine the effects of RHOJ on the EMT markers' expression of GC cells. The GC cells' migration and invasion were investigated by transwell assay. The tumor growth and metastasis were demonstrated correspondingly in different xenograft models. Results: Firstly, it was noticed that RHOJ was significantly upregulated in EMT-subtype GC and RHOJ has close relationships with the EMT process of GC, based on the Gene Expression Omnibus (GEO) and the Cancer Genome Atlas (TCGA) databases. Next, transwell assay and tail vein metastasis models were conducted to verify that RHOJ mediates the EMT to regulate the invasion and metastasis of GC in vitro and in vivo. In addition, weakened tumor angiogenesis was observed after RHOJ knockdown by the angiogenesis assay of HUVEC. RNA-seq and further study unveiled that RHOJ aggravates the malignant progression of GC by inducing EMT through IL-6/STAT3 to promote invasion and metastasis. Finally, blocking the IL-6/STAT3 signaling overcame RHOJ-mediated GC cells' growth and migration. Conclusions: These results indicate that the upregulation of RHOJ contributes to EMT-subtype GC invasion and metastasis via IL-6/STAT3 signaling, and RHOJ is expected to become a promising biomarker and therapeutic target for EMT-subtype GC patients. Ivyspring International Publisher 2023-08-21 /pmc/articles/PMC10535698/ /pubmed/37781036 http://dx.doi.org/10.7150/ijbs.81972 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Ma, Zhijie
Sun, Qi
Zhang, Chengfei
Zheng, Qian
Liu, Yixuan
Xu, Haojun
He, Yiting
Yao, Chengyun
Chen, Jinfei
Xia, Hongping
RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer
title RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer
title_full RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer
title_fullStr RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer
title_full_unstemmed RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer
title_short RHOJ Induces Epithelial-to-Mesenchymal Transition by IL-6/STAT3 to Promote Invasion and Metastasis in Gastric Cancer
title_sort rhoj induces epithelial-to-mesenchymal transition by il-6/stat3 to promote invasion and metastasis in gastric cancer
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535698/
https://www.ncbi.nlm.nih.gov/pubmed/37781036
http://dx.doi.org/10.7150/ijbs.81972
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