Han Chunyao
Department of General Surgery, The Second Hospital of Shanxi Medical University, No. 382, Wuyi Road, Xinghualing District, Taiyuan City, Shanxi Province, China.
Sci Rep. 2025 Aug 23;15(1):31024. doi: 10.1038/s41598-025-16674-2.
The adaptor protein SRCIN1 is a novel Src-binding protein that regulates Src activation through C-terminal Src kinase. SRCIN1 has been shown to promote the development of colorectal cancer, while acting as a tumor suppressor in breast cancer. However, its role in the development of thyroid cancer has remained unknown. In this study, we analyzed the biological characteristics of SRCIN1 in thyroid cancer using public data (HPA, TIMER, GEPIA and UALCAN). Additionally, we investigated the biological impact of SRCIN1 knockdown and overexpression on thyroid cancer cells both in vitro and in vivo. Our results revealed that the expression of SRCIN1 was higher (more than twice) in thyroid cancer tissues than in normal tissues and was positively correlated with tumor stage (stage1 vs. stage4 p < 0.05). Suppression of SRCIN1 promoted cell apoptosis (at least onefold) and inhibited cell proliferation and migration (at least 50%), whereas overexpression had the opposite effect. Furthermore, our analysis indicated that SRCIN1 activates the Wnt/β-catenin signaling axis, as evidenced by increased levels of β-catenin, DVL2, Cyclin D1, c-Myc, and Axin2. TOP/FOP experiments also revealed that Wnt/β-catenin signaling was activated by SRCIN1. It is noteworthy that the specific knockdown of SRCIN1 results in a reduction of key downstream gene targets within the Wnt/β-catenin axis, and tumors in mice treated with SRCIN1-targeting siRNA exhibit significantly smaller volumes (reduction exceeding 50%). Taken together, our study highlights the clinical and therapeutic relevance of SRCIN1 in thyroid cancer and suggests it as a potential therapeutic target for this disease.
衔接蛋白SRCIN1是一种新型的Src结合蛋白，可通过C端Src激酶调节Src激活。已证明SRCIN1可促进结直肠癌的发展，同时在乳腺癌中发挥肿瘤抑制作用。然而，其在甲状腺癌发展中的作用尚不清楚。在本研究中，我们使用公共数据（HPA、TIMER、GEPIA和UALCAN）分析了SRCIN1在甲状腺癌中的生物学特性。此外，我们研究了SRCIN1基因敲低和过表达对甲状腺癌细胞的体内外生物学影响。我们的结果显示，SRCIN1在甲状腺癌组织中的表达高于正常组织（超过两倍），且与肿瘤分期呈正相关（1期与4期相比，p<0.05）。抑制SRCIN1可促进细胞凋亡（至少一倍），并抑制细胞增殖和迁移（至少50%），而过表达则产生相反的效果。此外，我们的分析表明，SRCIN1激活Wnt/β-连环蛋白信号轴，β-连环蛋白、DVL2、细胞周期蛋白D1、c-Myc和Axin2水平的升高证明了这一点。TOP/FOP实验也显示，SRCIN1激活了Wnt/β-连环蛋白信号。值得注意的是，特异性敲低SRCIN1会导致Wnt/β-连环蛋白轴内关键下游基因靶点的减少，用靶向SRCIN1的siRNA处理的小鼠肿瘤体积显著减小（减小超过50%）。综上所述，我们的研究突出了SRCIN1在甲状腺癌中的临床和治疗相关性，并表明它是这种疾病的潜在治疗靶点。
