Jiang Gui-Yang, Zhang Xiu-Peng, Wang Liang, Lin Xu-Yong, Yu Juan-Han, Wang En-Hua, Zhang Yong
Department of Pathology, First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China.
Department of Pathology, Cancer Hospital of China Medical University, Shenyang, China.
Tumour Biol. 2016 Oct;37(10):14311-14319. doi: 10.1007/s13277-016-5298-1. Epub 2016 Sep 5.
FBXO25 is a recently discovered protein that belongs to the Fbx class of the F-box family of proteins, and F-box proteins play a crucial role in tumorigenesis. However, the function of FBXO25 in cancer was not revealed so far. As measured by immunohistochemical staining, FBXO25 was highly expressed in the cytoplasm and nucleus of lung cancer samples (64.2 %, 136/212), compared with adjacent normal lung tissues (23.3 %, 7/30, p < 0.01). In addition, its expression was positively correlated with TNM staging (p < 0.001) and lymph node metastasis (p = 0.017). The overall survival of non-small-cell lung cancer (NSCLC) patients with FBXO25-positive expression (40.646 ± 1.745 months) was significantly reduced compared with those with FBXO25-negative expression (46.548 ± 2.176 months, p = 0.023). Consistently, we found that the proliferation, invasion, and migration capacity of A549 cells transfected with FBXO25 were significantly greater than those of control cells, while interference of FBXO25 could significantly inhibit cell proliferation, invasion, and migration in H1299 cells. Furthermore, we demonstrated that FBXO25 could regulate the expression of β-catenin, YAP, some cyclins, and matrix metalloproteinases (MMPs). Collectively, these results indicate that FBXO25 may promote the tumorigenicity of lung cancer cells and might serve as a novel therapeutic target of NSCLC.
FBXO25是一种最近发现的蛋白质，属于F-box蛋白家族的Fbx类别，而F-box蛋白在肿瘤发生中起着关键作用。然而，到目前为止FBXO25在癌症中的功能尚未明确。通过免疫组织化学染色检测，与相邻正常肺组织（23.3%，7/30，p<0.01）相比，FBXO25在肺癌样本的细胞质和细胞核中高表达（64.2%，136/212）。此外，其表达与TNM分期（p<0.001）和淋巴结转移（p=0.017）呈正相关。FBXO25阳性表达的非小细胞肺癌（NSCLC）患者的总生存期（40.646±1.745个月）与FBXO25阴性表达的患者（46.548±2.176个月，p=0.023）相比显著缩短。一致地，我们发现转染FBXO25的A549细胞的增殖、侵袭和迁移能力明显高于对照细胞，而干扰FBXO25可显著抑制H1299细胞的增殖、侵袭和迁移。此外，我们证明FBXO25可以调节β-连环蛋白、YAP、一些细胞周期蛋白和基质金属蛋白酶（MMPs）的表达。总体而言，这些结果表明FBXO25可能促进肺癌细胞的致瘤性，并可能作为NSCLC的一个新的治疗靶点。
