含Src同源2结构域转化蛋白C3（SHC3）在结直肠癌中的表达、预后价值及其潜在作用
The expression and prognostic value of Src homology 2 domain-containing transforming protein C3 (SHC3) and its potential role in colorectal cancer.
作者信息
Zhao Chedong, Zhang Jian, Ma Jing, Zhang Ning, Chen Wei
机构信息
Department of Clinical Laboratory, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Dermatology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
出版信息
Transl Cancer Res. 2021 Jul;10(7):3418-3428. doi: 10.21037/tcr-21-294.
BACKGROUND
To determine the prognostic value of Src homology 2 domain-containing transforming protein C3 (SHC3) in colorectal cancer (CRC).
METHODS
The pan-cancer expression of SHC3 mRNA in TCGA was analyzed using Gene_DE module in Tumor Immune Estimation Resource (TIMER) database. SHC3 mRNA expression in CRC was further analyzed by TCGA and Oncomine databases. The dataset from Kaplan-Meier Plotter (http://kmplot.com) was used to analyze the overall survival (OS) of CRC patients in relationship of SHC3 expression. SHC3 mRNA expression in the CRC HCT116 and RKO cell lines was measured by qRT-PCR. Both cell lines were transduced with shSHC3 or shCtrl lentiviruses, and the knockdown was validated by qRT-PCR and Western blotting. The effects of SHC3 knockdown were analyzed by MTT assay, Celigo-based cell counting, colony formation assay, scratch assay and Transwell migration assay.
RESULTS
SHC3 is upregulated in tumor tissues relative to normal tissues across multiple cancer types including CRC in TCGA database, and associated with poor OS (HR =3.27, 95% CI: 1.31-8.16, log-rank P=0.0072). Consistent with this, SHC3 mRNA levels were significantly high in CRC cell lines. SHC3 knockdown in the HCT116 and RKO cells markedly reduced their proliferation and migration, and promoted apoptosis.
CONCLUSIONS
SHC3 is upregulated in CRC tissues and cell lines, and likely functions as an oncogene in CRC.
背景
确定含Src同源2结构域的转化蛋白C3（SHC3）在结直肠癌（CRC）中的预后价值。
方法
使用肿瘤免疫评估资源（TIMER）数据库中的Gene_DE模块分析TCGA中SHC3 mRNA的泛癌表达。通过TCGA和Oncomine数据库进一步分析CRC中SHC3 mRNA的表达。使用来自Kaplan-Meier Plotter（http://kmplot.com）的数据集分析CRC患者的总生存期（OS）与SHC3表达的关系。通过qRT-PCR测量CRC HCT116和RKO细胞系中SHC3 mRNA的表达。用shSHC3或shCtrl慢病毒转导这两种细胞系，并通过qRT-PCR和蛋白质印迹法验证敲低效果。通过MTT法、基于Celigo的细胞计数、集落形成试验、划痕试验和Transwell迁移试验分析SHC3敲低的影响。
结果
在TCGA数据库中，相对于包括CRC在内的多种癌症类型的正常组织，肿瘤组织中SHC3上调，并且与较差的OS相关（HR = 3.27，95% CI：1.31 - 8.16，对数秩检验P = 0.0072）。与此一致，CRC细胞系中SHC3 mRNA水平显著升高。HCT116和RKO细胞中SHC3的敲低显著降低了它们的增殖和迁移，并促进了细胞凋亡。
结论
SHC3在CRC组织和细胞系中上调，并且可能在CRC中作为癌基因发挥作用。
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