Huang Chengzhi, Yi Hui, Zhou Yue, Zhang Qing, Yao Xueqing
School of Medicine, South China University of Technology, Guangzhou 510006, China.
Department of Gastrointestinal Surgery, Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
Cancers (Basel). 2022 Jul 31;14(15):3735. doi: 10.3390/cancers14153735.
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.
SH3结构域和四肽重复序列2（SH3TC2）是一个蛋白质编码基因，此前已被描述为神经疾病的关键信号枢纽。尽管越来越多的证据支持SH3TC2在各类癌症的肿瘤发生中起着至关重要的作用，但目前尚无对SH3TC2的系统分析。其在其他癌症中的功能和机制仍不清楚。因此，本研究旨在分析SH3TC2在各类癌症中的情况，以发现其在一种或多种特定癌症中的致瘤作用。在本研究中，我们在TCGA - GTEx泛癌数据集中分析了SH3TC2在不同肿瘤中的表达水平和预后价值。随后，通过临床样本以及体外和体内实验，进一步探究了SH3TC2在结直肠癌（CRC）中的预后作用和机制。我们观察到SH3TC2在结肠腺癌（COAD）、急性髓系白血病（LAML）、直肠癌（READ）、皮肤黑色素瘤（SKCM）和睾丸生殖细胞肿瘤（TGCT）中存在差异表达。随后，SH3TC2在CRC、LAML和SKCM的临床分期和预后价值方面显示出显著影响。此外，我们在TCGA数据库和七个GEO数据集中发现，SH3TC2在肿瘤组织中显著高表达。通过对SH3TC2及其共表达基因的富集分析，我们发现SH3TC2可能在MAPK信号通路中发挥作用。相关性分析表明，SH3TC2与MAPK信号通路中的多个关键因子显著相关。此外，在我们包含40例CRC患者的队列中，肿瘤组织中发现SH3TC2表达较高。SH3TC2的过表达可能意味着预后不良。敲低SH3TC2显著抑制肿瘤侵袭、迁移和增殖。更重要的是，敲低SH3TC2可抑制CRC小鼠模型中的肿瘤生长。本研究初步对SH3TC2进行了泛癌研究，并进一步探究了其在CRC中的作用机制。我们的研究表明，SH3TC2的高表达可能通过MAPK信号通路促进CRC进展和侵袭。
