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RBMS1-HSPA8轴激活驱动头颈鳞状细胞癌进展。

RBMS1-HSPA8 axis activation drives head and neck squamous cell carcinoma progression.

作者信息

Yin Xinghong, Luo Meng, Zha Xiaojun, Duan Maoli, Liu Yehai

机构信息

Department of Otorhinolaryngology Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, Anhui Province, 230000, China.

Department of Otorhinolaryngology Head & Neck Surgery, Fuyang People's Hospital, Fuyang, China.

出版信息

BMC Cancer. 2025 Mar 27;25(1):549. doi: 10.1186/s12885-025-13937-z.

DOI:10.1186/s12885-025-13937-z
PMID:40140757
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11948914/
Abstract

BACKGROUND

Head and Neck Squamous Cell Carcinoma (HNSCC) presents significant challenges in terms of treatment and prognosis, highlighting the urgent need for new therapeutic targets and the development of effective targeted therapies to enhance patient outcomes and survival.

METHODS

The expression level of RBMS1 in HNSCC was identified by GEO and TCGA databases through systematic bioinformatics analysis, and further verified in human specimens by quantitative Real-time PCR, Western blot, and immunohistochemistry. The results of CCK-8, colony formation assay, wound healing, Transwell, and tumor formation assays in nude mice showed that RBMS1 promoted the proliferation, migration, and invasion of HNSCC cells. The downstream target genes of RBMS1 were identified in the RBMS1 knockdown and the control groups of TU177 cells using RNA sequencing. HSPA8 was identified as a downstream target gene of RBMS1 in functional in vitro and tumor formation experiments in nude mice.

RESULTS

Elevated expression levels of RBMS1 in HNSCC were identified using relevant databases and validated in human specimens. In both in vitro and in vivo studies, overexpression of RBMS1 promoted the proliferation, migration, and invasion of HNSCC cells, whereas knockdown of RBMS1 significantly inhibited these processes. RNA sequencing analysis revealed HSPA8 as a downstream target of RBMS1, and rescue experiments confirmed that HSPA8 serves as a crucial intermediary in the regulatory pathway of tumor progression influenced by RBMS1.

CONCLUSIONS

This study suggests that RBMS1 regulates HSPA8 to promote the proliferation, migration, and invasion of HNSCC cells, making it a potential therapeutic target for HNSCC.

摘要

背景

头颈部鳞状细胞癌(HNSCC)在治疗和预后方面面临重大挑战,凸显了对新治疗靶点的迫切需求以及开发有效的靶向治疗以改善患者预后和生存的必要性。

方法

通过系统的生物信息学分析,利用GEO和TCGA数据库确定HNSCC中RBMS1的表达水平,并通过定量实时PCR、蛋白质免疫印迹和免疫组织化学在人体标本中进一步验证。CCK-8、集落形成试验、伤口愈合试验、Transwell试验以及裸鼠肿瘤形成试验的结果表明,RBMS1促进了HNSCC细胞的增殖、迁移和侵袭。使用RNA测序在RBMS1敲低组和TU177细胞对照组中鉴定RBMS1的下游靶基因。在体外功能实验和裸鼠肿瘤形成实验中,HSPA8被鉴定为RBMS1的下游靶基因。

结果

利用相关数据库确定了HNSCC中RBMS1的表达水平升高,并在人体标本中得到验证。在体外和体内研究中,RBMS1的过表达均促进了HNSCC细胞的增殖、迁移和侵袭,而RBMS1的敲低则显著抑制了这些过程。RNA测序分析显示HSPA8是RBMS1的下游靶点,挽救实验证实HSPA8在RBMS1影响的肿瘤进展调控途径中起关键中介作用。

结论

本研究表明,RBMS1通过调节HSPA8促进HNSCC细胞的增殖、迁移和侵袭,使其成为HNSCC的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/41b49db418e9/12885_2025_13937_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/5f88be6edb2d/12885_2025_13937_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/7519ada7c318/12885_2025_13937_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/23d92bbe7ff6/12885_2025_13937_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/f8da73828b38/12885_2025_13937_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/e62beecfe9c3/12885_2025_13937_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/41b49db418e9/12885_2025_13937_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/5f88be6edb2d/12885_2025_13937_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/7519ada7c318/12885_2025_13937_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/23d92bbe7ff6/12885_2025_13937_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/f8da73828b38/12885_2025_13937_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/e62beecfe9c3/12885_2025_13937_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef41/11948914/41b49db418e9/12885_2025_13937_Fig6_HTML.jpg

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本文引用的文献

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HSPA8 dampens SCAP/INSIG split and SREBP activation by reducing PKR-mediated INSIG phosphorylation.热休克蛋白家族A成员8(HSPA8)通过减少蛋白激酶R(PKR)介导的胰岛素诱导基因(INSIG)磷酸化,抑制SREBP裂解激活蛋白(SCAP)/INSIG的分离以及固醇调节元件结合蛋白(SREBP)的激活。
Cell Rep. 2025 Mar 25;44(3):115339. doi: 10.1016/j.celrep.2025.115339. Epub 2025 Feb 19.
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RBMS1 interference inhibits malignant progression of glioblastoma cells and promotes ferroptosis.RBMS1干扰抑制胶质母细胞瘤细胞的恶性进展并促进铁死亡。
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Increased ANKRD1 Levels in Early Senescence Mediated by RBMS1-Elicited mRNA Stabilization.
早期衰老中 ANKRD1 水平的升高是由 RBMS1 引发的 mRNA 稳定介导的。
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The suppression of HSPA8 attenuates NLRP3 ubiquitination through SKP2 to promote pyroptosis in sepsis-induced lung injury.HSPA8的抑制通过SKP2减弱NLRP3泛素化,从而促进脓毒症诱导的肺损伤中的细胞焦亡。
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The Binding of HSPA8 and Mitochondrial ALDH2 Mediates Oxygen-Glucose Deprivation-Induced Fibroblast Senescence.热休克蛋白家族A成员8(HSPA8)与线粒体乙醛脱氢酶2(ALDH2)的结合介导氧糖剥夺诱导的成纤维细胞衰老。
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