A novel type of noncoding RNA, circRNA has been reported to participate in the occurrence and development of diseases through many mechanisms. The MAPK pathway is a common signal transduction pathway involved in cell proliferation, inflammation and apoptosis and plays a particularly important role in cancers. However, the role of circRNAs related to the MAPK pathway in gastric cancer has not been explored. A bioinformatics analysis was performed to profile and identify the circRNAs involved in the MAPK pathway in gastric cancer. The tumor-suppressive role of circMAPK1 was confirmed both in vitro and in vivo. Mass spectrometry, Western blot and immunofluorescence staining assays were used to validate the existence and expression of MAPK1–109aa. The molecular mechanism of circMAPK1 was investigated by mass spectrometry and immunoprecipitation analyses. In this study, we identified that circMAPK1 (hsa_circ_0004872) was downregulated in gastric cancer tissues compared with adjacent normal tissues. Importantly, lower circMAPK1 expression predicted poor survival in GC patients. CircMAPK1 inhibited the proliferation and invasion of gastric cancer cells in vitro and in vivo. Next, we found that circMAPK1 encoded a novel protein with 109 amino acids in length. Through a series of functional experiments, we confirmed that circMAPK1 exerted a tumor-suppressing effect via the encoded protein MAPK1–109aa. Mechanistically, the tumor suppressor MAPK1–109aa inhibited the phosphorylation of MAPK1 by competitively binding to MEK1, thereby suppressing the activation of MAPK1 and its downstream factors in MAPK pathway. Our study revealed that circMAPK1 inhibits the malignant biological behavior of gastric cancer cells through its encoded protein MAPK1–109aa. More importantly, circMAPK1 is a favorable predictor for gastric cancer patients and may provide a new therapeutic target in the treatment of gastric cancer.

中文翻译：

---

circMAPK1 编码的新型蛋白质通过抑制 MAPK 信号传导的激活来抑制胃癌的进展


circRNA是一种新型非编码RNA，已被报道通过多种机制参与疾病的发生和发展。 MAPK通路是参与细胞增殖、炎症和凋亡的常见信号转导通路，在癌症中发挥着尤为重要的作用。然而，与MAPK通路相关的circRNA在胃癌中的作用尚未被探索。通过生物信息学分析来分析和鉴定参与胃癌 MAPK 通路的 circRNA。 circMAPK1 的肿瘤抑制作用在体外和体内均得到证实。使用质谱、蛋白质印迹和免疫荧光染色测定来验证 MAPK1-109aa 的存在和表达。通过质谱和免疫沉淀分析研究了 circMAPK1 的分子机制。在这项研究中，我们发现与邻近正常组织相比，circMAPK1 (hsa_circ_0004872) 在胃癌组织中表达下调。重要的是，较低的 circMAPK1 表达预示着 GC 患者的生存率较差。 CircMAPK1在体外和体内抑制胃癌细胞的增殖和侵袭。接下来，我们发现circMAPK1编码一种长度为109个氨基酸的新蛋白质。通过一系列的功能实验，我们证实circMAPK1通过编码的蛋白MAPK1-109aa发挥肿瘤抑制作用。从机制上来说，抑癌基因MAPK1-109aa通过与MEK1竞争性结合来抑制MAPK1的磷酸化，从而抑制MAPK1及其下游因子的激活。我们的研究表明，circMAPK1通过其编码的蛋白MAPK1-109aa抑制胃癌细胞的恶性生物学行为。 更重要的是，circMAPK1是胃癌患者良好的预测因子，可能为胃癌的治疗提供新的治疗靶点。