Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway.

SH3 domain and tetrapeptide repeat 2 (SH3TC2) is a protein-encoding gene and has previously been described as a critical signaling hub for neurological disorders. Although increasing evidence supports a vital role of SH3TC2 in the tumorigenesis of various kinds of cancer, no systematic analysis of SH3TC2 is available. The function and mechanism of in other cancers remain unknown. Thus, this study aimed to analyze SH3TC2 in various kinds of cancer to find its tumorigenic role in one or more specific cancers. In the current study, we analyzed the expression level and prognostic value of in different tumors in the TCGA-GTEx pan-cancer dataset. Subsequently, the prognostic role and mechanism of in colorectal cancer (CRC) were further explored via clinical samples and in vitro and in vivo experiments. We observed differential expression of in colon adenocarcinoma (COAD), acute myeloid leukemia (LAML), READ (rectum adenocarcinoma), SKCM (skin cutaneous melanoma), and TGCT (testicular germ cell tumors). Subsequently, showed a significant effect on the clinical stage and prognostic value in CRC, LAML, and SKCM. Moreover, we found in the TCGA database and seven GEO datasets that was significantly highly expressed in tumor tissue. Through enrichment analysis of and its co-expressed genes, we found that may play a role in the MAPK signaling pathway. Correlation analysis indicated that was significantly associated with multiple key factors in the MAPK signaling pathway. Additionally, higher expression of SH3TC2 was found in tumor tissue in our cohort including 40 CRC patients. Overexpression of SH3TC2 may imply poor prognosis. Knockdown of significantly inhibited tumor invasion, migration, and proliferation. More importantly, knockdown of inhibited tumor growth in a CRC mouse model. The study preliminarily conducted a pan-cancer study of and further explored the mechanism of in CRC. Our research revealed that higher expression of may promote CRC progression and invasion via the MAPK signaling pathway.