Sun Jing, Zhang Xiupeng, Sun Yefei
Department of Gastroenterology, the First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Pathology, the First Affiliated Hospital of China Medical University, Shenyang, China.
J Mol Histol. 2023 Apr;54(2):135-145. doi: 10.1007/s10735-023-10117-w. Epub 2023 Mar 29.
Chromosome 1 open reading frame 109 (C1orf09) is a protein whose expression pattern and biological function in humans, particularly in malignant tumors, have not been explored. In this study, both bioinformatics and immunohistochemical staining revealed that C1orf109 was overexpressed in the cytoplasm of liver cancer cells, and the positive ratio of C1orf109 in liver cancer samples (42.5%, 37/87) was significantly higher than that in normal liver tissues (10%, 3/30, P = 0.0012). C1orf109 expression was correlated with an advanced TNM stage (P = 0.017) and vascular invasion (P = 0.023) and predicted the poor overall survival of patients with liver cancer (P = 0.001). C1orf109 facilitated tumor growth, colony formation, migration, and invasion by activating Wnt signaling by upregulating non-phosphorylated β-catenin and its downstream target genes such as CyclinD1, c-myc, and MMP7. Our results also suggest that C1orf109 interacts and co-localizes with casein kinase II (CK2) to activate Wnt signaling. Treatment with a CK2-specific inhibitor markedly counteracted the increased expression of CyclinD1, c-Myc, and MMP7, as well as the upregulation of tumor proliferation and invasion caused by C1orf109 overexpression. Taken together, our results indicate that C1orf109 accelerates liver cancer cell proliferation and invasion by strengthening the Wnt signaling pathway in a CK2-dependent manner.
1号染色体开放阅读框109（C1orf09）是一种蛋白质，其在人类尤其是恶性肿瘤中的表达模式和生物学功能尚未得到探索。在本研究中，生物信息学和免疫组织化学染色均显示，C1orf109在肝癌细胞的细胞质中过表达，肝癌样本中C1orf109的阳性率（42.5%，37/87）显著高于正常肝组织（10%，3/30，P = 0.0012）。C1orf109表达与TNM分期进展（P = 0.017）和血管侵犯（P = 0.023）相关，并预测肝癌患者的总体生存率较差（P = 0.001）。C1orf109通过上调非磷酸化β-连环蛋白及其下游靶基因如细胞周期蛋白D1、c-myc和基质金属蛋白酶7来激活Wnt信号通路，从而促进肿瘤生长、集落形成、迁移和侵袭。我们的结果还表明，C1orf109与酪蛋白激酶II（CK2）相互作用并共定位以激活Wnt信号通路。用CK2特异性抑制剂处理可显著抵消细胞周期蛋白D1、c-Myc和基质金属蛋白酶7的表达增加，以及C1orf109过表达引起的肿瘤增殖和侵袭上调。综上所述，我们的结果表明，C1orf109通过以CK2依赖的方式增强Wnt信号通路来加速肝癌细胞的增殖和侵袭。
