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RhoB 的下调抑制宫颈癌的进展并增强顺铂敏感性。

Downregulation of RhoB Inhibits Cervical Cancer Progression and Enhances Cisplatin Sensitivity.

机构信息

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave, Wuhan 430030, China.

出版信息

Genes (Basel). 2024 Sep 10;15(9):1186. doi: 10.3390/genes15091186.

DOI:10.3390/genes15091186
PMID:39336777
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11431011/
Abstract

RhoB, a member of the Rho GTPase family, has been implicated in the malignant progression of various cancer types. However, its role in cervical cancer (CC) remains unclear. Therefore, this study aims to elucidate the biological function of RhoB in CC and its relationship with cisplatin sensitivity. We analyzed data from the TCGA, GTEx, and GEO databases, revealing that mRNA expression is downregulated in CC tissues compared to normal cervical tissues. The further analysis of the TCGA database and Tongji samples showed that CC patients with a high RhoB expression had a shorter overall survival (OS). Subsequently, we found that the knockdown of RhoB inhibited the proliferation, migration, and invasion of cancer cells, while increasing apoptosis. Through Western blot (WB) analysis, we found that knocking down RhoB resulted in an increased expression of the epithelial marker E-cadherin, while the levels of N-cadherin, MMP2, MMP9, Vimentin, and Snail1 were reduced. Additionally, mRNA expression was upregulated in CC tissues after chemotherapy compared to CC tissues before chemotherapy. In CC cells, RhoB expression increased with cisplatin concentration, and the IC50 value decreased following RhoB knockdown. Moreover, the knockdown of RhoB could enhance the cellular apoptosis triggered by cisplatin. This study demonstrated that RhoB plays an oncogenic role in CC and that its knockdown could enhance the sensitivity of CC cells to cisplatin.

摘要

RhoB,Rho GTPase 家族的一员,与多种癌症类型的恶性进展有关。然而,其在宫颈癌(CC)中的作用尚不清楚。因此,本研究旨在阐明 RhoB 在 CC 中的生物学功能及其与顺铂敏感性的关系。我们分析了 TCGA、GTEx 和 GEO 数据库中的数据,结果表明 RhoB mRNA 在 CC 组织中的表达低于正常宫颈组织。对 TCGA 数据库和同济样本的进一步分析表明,RhoB 高表达的 CC 患者总生存期(OS)更短。随后,我们发现 RhoB 的敲低抑制了癌细胞的增殖、迁移和侵袭,同时增加了细胞凋亡。通过 Western blot(WB)分析,我们发现 RhoB 的敲低导致上皮标志物 E-钙黏蛋白的表达增加,而 N-钙黏蛋白、MMP2、MMP9、波形蛋白和 Snail1 的水平降低。此外,与化疗前的 CC 组织相比,化疗后 CC 组织中 RhoB mRNA 的表达上调。在 CC 细胞中,RhoB 的表达随着顺铂浓度的增加而增加,并且在 RhoB 敲低后 IC50 值降低。此外,RhoB 的敲低可以增强顺铂引发的细胞凋亡。这项研究表明,RhoB 在 CC 中发挥致癌作用,敲低 RhoB 可以增强 CC 细胞对顺铂的敏感性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/713d6f6ff48d/genes-15-01186-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/8a53781d8a5a/genes-15-01186-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/b8c6e3f930cd/genes-15-01186-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/668ae2457391/genes-15-01186-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/435dbc42e400/genes-15-01186-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/e56166e77f6c/genes-15-01186-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/713d6f6ff48d/genes-15-01186-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/8a53781d8a5a/genes-15-01186-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/b8c6e3f930cd/genes-15-01186-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/668ae2457391/genes-15-01186-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/435dbc42e400/genes-15-01186-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/e56166e77f6c/genes-15-01186-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/928e/11431011/713d6f6ff48d/genes-15-01186-g006.jpg

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本文引用的文献

1
RhoB expression associated with chemotherapy response and prognosis in colorectal cancer.RhoB表达与结直肠癌的化疗反应及预后相关。
Cancer Cell Int. 2024 Feb 15;24(1):75. doi: 10.1186/s12935-024-03236-1.
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Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative.2020 年全球宫颈癌发病率和死亡率估计:世卫组织全球消除宫颈癌倡议的基线分析。
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Sequential gene expression analysis of cervical malignant transformation identifies RFC4 as a novel diagnostic and prognostic biomarker.
连续的宫颈癌恶性转化基因表达分析鉴定 RFC4 为一种新的诊断和预后生物标志物。
BMC Med. 2022 Nov 9;20(1):437. doi: 10.1186/s12916-022-02630-8.
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The prognostic value and biological significance of gap junction beta protein 2 (GJB2 or Cx26) in cervical cancer.缝隙连接β蛋白2(GJB2或Cx26)在宫颈癌中的预后价值及生物学意义
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Hsa-miR-3178/RhoB/PI3K/Akt, a novel signaling pathway regulates ABC transporters to reverse gemcitabine resistance in pancreatic cancer.hsa-miR-3178/RhoB/PI3K/Akt,一个新的信号通路调节 ABC 转运体逆转胰腺癌中吉西他滨耐药性。
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The Critical Role of Dysregulated RhoB Signaling Pathway in Radioresistance of Colorectal Cancer.失调的 RhoB 信号通路在结直肠癌放射抵抗中的关键作用。
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