Guo Yinmou, Wang Yumei, Ma Yali, Chen Gongbin, Yue Peiru, Li Yang
The First Ward, Department of Oncology, The First People's Hospital of Shangqiu City Shangqiu 476100 China
Department of Pediatrics, The First People's Hospital of Shangqiu City Shangqiu 476100 China.
RSC Adv. 2020 Feb 7;10(10):6006-6016. doi: 10.1039/c9ra09497k. eCollection 2020 Feb 4.
Gastric cancer (GC) is one type of the most common malignancies in the world. In the process of exploring the pathological mechanism of GC and searching for treatment methods, long non-coding RNAs (lncRNAs) display significant participation. Small ubiquitin-like modifier 1 pseudogene 3 (SUMO1P3) is a newly identified lncRNA, of which the biological role and underlying mechanism in GC progression have not been elucidated. Here, through the comparisons between GC patients' tumor and normal tissue samples, as well as normal gastric mucosal and GC cell lines, we confirmed a significant upregulation of SUMO1P3 in GC tissues and cell lines. Meanwhile, significant upregulation of SUMO1P3 was observed in advanced GC patients, and patients with high level of SUMO1P3 displayed a poor survival rate. Next, gain- and loss-of-function experiments were performed in GC cells, and the results exhibited that SUMO1P3 positively regulated proliferation and invasion of GC cells. Then, we constructed drug-resistant GC cell strains and explore the role of SUMO1P3 in the resistance of GC cells to cisplatin (DDP) and 5-fluorouracil (5-Fu). Finally, bioinformatics analysis and RNA pull-down assay demonstrated that SUMO1P3 could directly interact with cellular nucleic acid binding protein (CNBP), thus positively regulating CNBP downstream oncogenes c-myc and cyclin D1 (CCND1). Our findings indicate that SUMO1P3 promotes proliferation, invasion and drug resistance of GC cells by interacting with CNBP, which reveals a potential prognostic biomarker and a novel therapeutic target for GC.
胃癌（GC）是世界上最常见的恶性肿瘤之一。在探索胃癌的病理机制和寻找治疗方法的过程中，长链非编码RNA（lncRNAs）发挥了重要作用。小泛素样修饰物1假基因3（SUMO1P3）是一种新发现的lncRNA，其在胃癌进展中的生物学作用和潜在机制尚未阐明。在此，通过比较胃癌患者的肿瘤组织与正常组织样本，以及正常胃黏膜和胃癌细胞系，我们证实了SUMO1P3在胃癌组织和细胞系中显著上调。同时，在晚期胃癌患者中观察到SUMO1P3显著上调，SUMO1P3水平高的患者生存率较差。接下来，在胃癌细胞中进行了功能获得和功能丧失实验，结果表明SUMO1P3正向调节胃癌细胞的增殖和侵袭。然后，我们构建了耐药胃癌细胞株，并探讨了SUMO1P3在胃癌细胞对顺铂（DDP）和5-氟尿嘧啶（5-Fu）耐药中的作用。最后，生物信息学分析和RNA下拉试验表明，SUMO1P3可直接与细胞核酸结合蛋白（CNBP）相互作用，从而正向调节CNBP下游的癌基因c-myc和细胞周期蛋白D1（CCND1）。我们的研究结果表明，SUMO1P3通过与CNBP相互作用促进胃癌细胞的增殖、侵袭和耐药，这揭示了一种潜在的预后生物标志物和胃癌的新型治疗靶点。
