The expression and prognostic value of Src homology 2 domain-containing transforming protein C3 (SHC3) and its potential role in colorectal cancer

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.