SMU1 敲低抑制胃癌生长、迁移和侵袭并调节细胞周期。

SMU1 Knockdown Suppresses Gastric Carcinoma Growth, Migration, and Invasion and Modulates the Cell Cycle.

机构信息

Department of Cell Biology, National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, China.

National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Bio-targeting Theranostics, Guangxi Medical University, Nanning, China.

出版信息

Cancer Control. 2024 Jan-Dec;31:10732748241281716. doi: 10.1177/10732748241281716.

DOI:10.1177/10732748241281716

PMID:39236066

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11378178/

Abstract

INTRODUCTION

The role of SMU1 in DNA replication and RNA splicing is well-established, yet its specific function and dysregulated mechanisms in gastric cancer (GC) remain inadequately elucidated. This study seeks to investigate the potential oncogenic and progression-promoting effects of SMU1 in GC, with the ultimate goal of informing novel approaches for treatment and diagnosis.

METHODS

The study investigated the expression levels of SMU1 in GC and adjacent normal tissues by analyzing data from the TCGA (27 tissue pairs) and GEO (47 tissue pairs) databases. Immunohistochemistry was used to examine 277 tumor tissue and adjacent non-tumor tissue spots from GC tissue chips, along with relevant follow-up information. The study further assessed the proliferation, invasion, and migration capabilities of cells by manipulating SMU1 expression levels and conducting various assays, including CCK-8, EdU incorporation, colony formation, transwells, flow cytometry, and subcutaneous tumorigenesis assays.

RESULTS

Our study revealed a significant upregulation of SMU1 mRNA and protein levels in GC tissues compared to adjacent tissues. Univariate and multivariate Cox analysis demonstrated that elevated levels of SMU1 were independent prognostic factors for GC prognosis ( = 0.036). Additionally, median survival analysis indicated a significant association between high SMU1 expression and poor prognosis in GC patients ( = 0.0002). In experiments conducted both in vivo and in vitro, it was determined that elevated levels of SMU1 can enhance the proliferation, invasion, and migration of GC cells, whereas suppression of SMU1 can impede the progression of GC by modulating the G1/S checkpoint of the cell cycle.

CONCLUSIONS

Our research introduces the novel idea that SMU1 could serve as a prognostic marker for GC progression, influencing cell proliferation through cell cycle activation. These results offer valuable insights into the understanding, diagnosis, and management of gastric carcinoma.

摘要

简介

SMU1 在 DNA 复制和 RNA 剪接中的作用已得到充分证实，但它在胃癌（GC）中的具体功能和失调机制仍未得到充分阐明。本研究旨在探讨 SMU1 在 GC 中的致癌和促进进展作用，以期为治疗和诊断提供新的方法。

方法

通过分析 TCGA（27 对组织）和 GEO（47 对组织）数据库中的数据，研究了 SMU1 在 GC 及相邻正常组织中的表达水平。免疫组织化学检测了 GC 组织芯片 277 个肿瘤组织和相邻非肿瘤组织点，以及相关随访信息。通过操纵 SMU1 表达水平并进行各种检测，包括 CCK-8、EdU 掺入、集落形成、transwell、流式细胞术和皮下肿瘤生成实验，评估了细胞的增殖、侵袭和迁移能力。

结果

我们的研究表明，与相邻组织相比，GC 组织中 SMU1 mRNA 和蛋白水平显著上调。单因素和多因素 Cox 分析表明，SMU1 水平升高是 GC 预后的独立预后因素（ = 0.036）。此外，中位生存分析表明，SMU1 高表达与 GC 患者的不良预后显著相关（ = 0.0002）。在体内和体外实验中均发现，SMU1 水平升高可增强 GC 细胞的增殖、侵袭和迁移能力，而抑制 SMU1 可通过调节细胞周期的 G1/S 检查点来阻碍 GC 的进展。