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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 SH3TC2 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 SH3TC2 in different tumors in the TCGA-GTEx pan-cancer dataset. Subsequently, the prognostic role and mechanism of SH3TC2 in colorectal cancer (CRC) were further explored via clinical samples and in vitro and in vivo experiments. We observed differential expression of SH3TC2 in colon adenocarcinoma (COAD), acute myeloid leukemia (LAML), READ (rectum adenocarcinoma), SKCM (skin cutaneous melanoma), and TGCT (testicular germ cell tumors). Subsequently, SH3TC2 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 SH3TC2 was significantly highly expressed in tumor tissue. Through enrichment analysis of SH3TC2 and its co-expressed genes, we found that SH3TC2 may play a role in the MAPK signaling pathway. Correlation analysis indicated that SH3TC2 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 SH3TC2 significantly inhibited tumor invasion, migration, and proliferation. More importantly, knockdown of SH3TC2 inhibited tumor growth in a CRC mouse model. The study preliminarily conducted a pan-cancer study of SH3TC2 and further explored the mechanism of SH3TC2 in CRC. Our research revealed that higher expression of SH3TC2 may promote CRC progression and invasion via the MAPK signaling pathway.<\/jats:p>","DOI":"10.3390\/cancers14153735","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T21:49:02Z","timestamp":1659304142000},"page":"3735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pan-Cancer Analysis Reveals SH3TC2 as an Oncogene for Colorectal Cancer and Promotes Tumorigenesis via the MAPK Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Chengzhi","family":"Huang","sequence":"first","affiliation":[{"name":"School of Medicine, South China University of Technology, Guangzhou 510006, China"},{"name":"Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"},{"name":"Department of General Surgery, Guangdong Provincial People\u2019s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou 341000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"},{"name":"Department of General Surgery, Guangdong Provincial People\u2019s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou 341000, China"},{"name":"School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China"},{"name":"Department of Pharmacology, The First People\u2019s Hospital of Zhaoqing, Zhaoqing 526000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"},{"name":"Department of General Surgery, Guangdong Provincial People\u2019s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou 341000, China"},{"name":"The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Guangdong Provincial People\u2019s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou 341000, China"},{"name":"Department of Gastrointestinal and Anorectal Surgery, The First People\u2019s Hospital of Zhaoqing, Zhaoqing 526000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0570-7585","authenticated-orcid":false,"given":"Xueqing","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Medicine, South China University of Technology, Guangzhou 510006, China"},{"name":"Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China"},{"name":"Department of General Surgery, Guangdong Provincial People\u2019s Hospital Ganzhou Hospital (Ganzhou Municipal Hospital), Ganzhou 341000, China"},{"name":"School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China"},{"name":"The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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