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富丝氨酸/精氨酸剪接因子7的表达在肝细胞癌中的意义OACSTPCD

Significance of expression of serine/arginine-rich splicing factor 7 in hepatocellular carcino-ma

中文摘要英文摘要

目的:探讨富丝氨酸/精氨酸剪接因子7(SRSF7)表达肝细胞癌(HCC)中的临床意义及生物学功能.方法:首先通过TCGA数据库中HCC转录组数据和临床数据分析SRSF7的表达水平、临床病理特征、功能和通路富集情况.再利用临床HCC样本、Huh7、Hep3B细胞株进行验证;将细胞分为对照组(control组)、过表达组(SRSF7OE组)和敲低组(SRSF7KD组).细胞计数试剂盒(CCK-8)实验、TUNEL实验检测其增殖和凋亡能力;伤口愈合实验、Transwell迁移实验和Transwell侵袭实验检测其迁移和侵袭能力;蛋白质免疫印迹法(western blotting)实验检测上皮—间质转化(EMT)相关标志物的蛋白水平;实时荧光定量PCR(RT-qPCR)实验检测SRSF7下游调控基因的mRNA水平.结果:生信分析结果显示,SRSF7在HCC肿瘤组织中呈高表达并且与肿瘤分级、分期和患者预后不良有关(P<0.05).Western blotting和免疫组化结果显示,SRSF7在肿瘤组织中呈高表达(P<0.05).与对照组相比,过表达SRSF7能促进HCC细胞增殖、迁移侵袭以及EMT进程;敲低SRSF7能抑制HCC细胞增殖、促进细胞凋亡,抑制HCC细胞迁移侵袭和EMT进程(P<0.05).结论:SRSF7在HCC中呈高表达,其高表达可能通过调控PAK5、RTL1等下游靶基因的表达来促进HCC细胞增殖,抑制细胞凋亡,并通过促进EMT进程来促进细胞迁移和侵袭,进而促进HCC的进展.

Objective:To investigate the clinical significance and biological functions of serine/arginine-rich splicing factor 7(SRSF7)expression in hepatocellular carcinoma(HCC).Methods:Firstly,the expression levels,clinical pathological features,functions,and pathway enrichment of SRSF7 were analyzed using HCC transcrip-tome and clinical data from TCGA database.Validation was then conducted using clinical HCC samples,Huh7,and Hep3B cell lines,which were divided into control group,overexpression group(SRSF7OE group),and knock-down group(SRSF7KD group).Proliferation and apoptosis abilities were assessed using cell counting kit-8(CCK-8)and TUNEL assays.Migration and invasion abilities were evaluated using wound healing,Transwell migra-tion,and Transwell invasion assays.Epithelial-mesenchymal transition(EMT)-related markers'protein levels were determined by western blotting,while reverse transcription-quantitative PCR(RT-qPCR)was utilized to measure the mRNA levels of downstream regulatory genes of SRSF7.Results:Bioinformatics analysis revealed that SRSF7was highly expressed in HCC tumor tissues and was associated with tumor grade,stage,and poor prognosis(P<0.05).Western blotting and immunohistochemical results showed that SRSF7 was highly ex-pressed in tumor tissues(P<0.05).Compared with the control group,overexpression of SRSF7 promoted the pro-liferation,migration,invasion and EMT process of HCC cells;knockdown of SRSF7 could inhibit HCC cell pro-liferation,promote cell apoptosis,and inhibit HCC cell migration,invasion and EMT process(P<0.05).Conclu-sion:SRSF7 is highly expressed in HCC,and its elevated expression may promote HCC cell proliferation and in-hibit cell apoptosis by regulating the expression of downstream target genes such as PAK5and RTL1,and pro-mote cell migration and invasion by promoting EMT process,ultimately promoting HCC progression.

唐文;张飞云;韦彩妮;赵玉玲;刘耀鸿;黎东心;黄秒;胡启平

广西医科大学基础医学院细胞生物学与遗传学教研室,南宁 530021||广西高校生物分子医学研究重点实验室,南宁 530021广西医科大学第一临床医学院,南宁 530021广西医科大学附属肿瘤医院影像诊断中心,南宁 530021广西医科大学基础医学院细胞生物学与遗传学教研室,南宁 530021||广西医科大学长寿与老年相关疾病教育部重点实验室,南宁 530021

临床医学

肝细胞癌富丝氨酸/精氨酸剪接因子7增殖迁移侵袭上皮—间质转化

hepatocellular carcinomaserine/arginine-rich splicing factor 7proliferationmigration and inva-sionepithelial-mesenchymal transition

《广西医科大学学报》 2024 (005)

697-707 / 11

国家自然科学基金资助项目(No.81760424);广西自然科学基金资助项目(2024GXNSFAA010034);广西医科大学2022年大学生创业训练计划立项项目资助(No.S202210598062)

10.16190/j.cnki.45-1211/r.2024.05.009

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