富含丝氨酸/精氨酸剪接因子6调控小细胞肺癌增殖和转移的机制研究  

The mechanism of serine/arginine-rich splicing factor 6 regulating the proliferation and metastasis of small cell lung cancer

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作  者:张梦珠 杜雯雯 黄建安[1] ZHANG Mengzhu;Du Wenwen;HUANG Jianan(Department of Respiratory and Critical Care Medicine,The First Affiliated Hospital of Soochow University,Soochow University,Suzhou,Jiangsu 215000,China)

机构地区:[1]苏州大学附属第一医院呼吸与危重症学科/苏州大学呼吸疾病研究所,江苏苏州215000

出  处:《临床肺科杂志》2025年第3期402-406,共5页Journal of Clinical Pulmonary Medicine

基  金:姑苏卫生人才科研项目(GSWS2021001)。

摘  要:目的研究富含丝氨酸/精氨酸剪接因子6(Serine/arginine-rich splicing factor 6,SRSF6)在小细胞肺癌增殖和转移中的作用及其机制。方法利用生物信息学方法,通过GEO数据库分析SRSF6在正常组织和小细胞肺癌(small cell lung cancer,SCLC)癌组织中的表达水平;qRT-PCR和Western Blot检测SRSF6在SCLC细胞株中的表达水平。利用小RNA干扰技术降低H446细胞中SRSF6表达,CCK-8实验检测对照组和干扰SRSF6组中SCLC细胞的增殖能力,Transwell实验验证对照组和干扰SRSF6组中SCLC细胞的迁移、侵袭能力。通过cBioportal数据库分析SRSF6与上皮间充质转化(Epithelial-mesenchymal transition,EMT)标志物E钙粘蛋白(E-cadherin)的表达相关性,利用Western Blot检测在小细胞肺癌细胞株内干扰SRSF6对EMT信号通路相关蛋白的影响。结果GEO数据库分析表明,SCLC患者组织中SRSF6的表达水平显著高于正常组织;qRT-PCR和Western Blot结果表明,SCLC细胞株H446与H82中SRSF6的表达水平显著高于正常肺上皮细胞BEAS-2B;CCK8实验显示干扰SRSF6后,细胞的增殖能力下降;Transwell实验发现干扰SRSF6后细胞的迁移、侵袭能力明显下降;cBioportal数据库分析显示,SRSF6与EMT标志物E-cadherin表达具有显著负相关(P<0.05)。Western Blot结果显示干扰SRSF6后E-cadherin蛋白表达上调,同时Snail、Slug蛋白表达下调。结论SRSF6在SCLC中高表达,与SCLC的增殖、转移密切相关,并通过调控EMT过程促进细胞转移。Objective To investigate the role and mechanism of Serine/Arginine-Rich Splicing factor 6(SRSF6)in the proliferation and metastasis of small cell lung cancer.Methods The expression level of SRSF6 in normal tissues and small cell lung cancer(SCLC)tissues was analyzed by the GEO database.The expression level of SRSF6 in SCLC cell lines was detected by qRT-PCR and Western Blot.CCK-8 assay was used to detect the proliferation ability of SCLC cells in the control group and the SRSF6 interference group.Transwell assay was used to verify the metastasis and invasion ability of SCLC cells in the control group and the SRSF6 interference group.The correlation between SRSF6 and E-cadherin,a marker of Epithelial-mesenchymal transition(EMT),was analyzed by cBioportal database.Western Blot was used to detect the effect of SRSF6 interference on EMT signaling pathway-related proteins in SCLC cell lines.Results Analysis of the GEO database showed that the expression of SRSF6 in SCLC tissues was significantly higher than that in normal tissues.qRT-PCR and Western Blot results showed that SRSF6 expression was significantly increased in SCLC cell lines H446 and H82 compared with normal lung epithelial cells BEAS-2B.CCK8 assay showed that knockdown of SRSF6 inhibited cell proliferation.Transwell assay showed that the ability of migration and invasion of SRSF6 knockdown cells was significantly decreased.cBioportal database analysis showed that SRSF6 was negatively correlated with the expression of EMT-related protein E-cadherin(P<0.05).The results of Western Blot showed that the expression of E-cadherin protein was up-regulated after interfering with SRSF6,and the expression of Snail and Slug protein was down-regulated.Conclusion SRSF6 is highly expressed in SCLC and is closely related to the proliferation and metastasis of SCLC,and promotes cell metastasis by regulating the EMT process.

关 键 词:富含丝氨酸/精氨酸剪接因子6 小细胞肺癌 增殖 转移 上皮间充质转化 

分 类 号:R734.2[医药卫生—肿瘤]

 

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