Guo Zijun, Guo Lin
Department of Operating Room, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
Transl Oncol. 2023 Dec;38:101791. doi: 10.1016/j.tranon.2023.101791. Epub 2023 Sep 21.
Gastric carcinoma has a poor prognosis and low survival rate. PRIM1 is closely associated with the origin of DNA replication and serves as a carcinogenic factor in multiple tumors. This study aimed to explore the functions of PRIM1 in the progression of gastric carcinoma. The luciferase reporter assay examined the regulatory effect of YAP1/TEAD4 on PRIM1. A xenograft tumor mouse model was constructed to observe cancer cell proliferation in vivo. The upregulation of PRIM1 was found in gastric carcinoma cells and tissues, and it was associated with poor prognosis. Silencing PRIM1 inhibited cell proliferation, arrested the cell cycle, and upregulated Cdc25, Cyclin B, and Cdc2 expression. In addition, apoptosis was increased upon PRIM1 knockdown, accompanied by increased protein levels of cleaved caspase-3 and caspase-8. In vivo, knockdown of PRIM1 suppressed the growth of xenograft tumors formed by gastric carcinoma cells. Moreover, PRIM1 silencing elevated the chemosensitivity of gastric carcinoma cells. By investigating molecular events downstream of the Hippo signaling pathway, we found that PRIM1 was a target gene of the YAP1/TEAD4 transcriptional regulatory complex. PRIM1 represents a novel target for gastric carcinoma therapeutic approaches.
胃癌预后较差，生存率低。PRIM1与DNA复制起点密切相关，是多种肿瘤中的致癌因素。本研究旨在探讨PRIM1在胃癌进展中的作用。荧光素酶报告基因检测法检测了YAP1/TEAD4对PRIM1的调控作用。构建了异种移植瘤小鼠模型以观察体内癌细胞增殖情况。发现PRIM1在胃癌细胞和组织中上调，且与预后不良相关。沉默PRIM1可抑制细胞增殖、使细胞周期停滞，并上调Cdc25、细胞周期蛋白B和Cdc2的表达。此外，PRIM1敲低后细胞凋亡增加，同时裂解的caspase-3和caspase-8蛋白水平升高。在体内，敲低PRIM1可抑制胃癌细胞形成的异种移植瘤的生长。此外，PRIM1沉默提高了胃癌细胞的化学敏感性。通过研究Hippo信号通路下游的分子事件，我们发现PRIM1是YAP1/TEAD4转录调控复合物的靶基因。PRIM1是胃癌治疗方法的一个新靶点。
