Tan Yeru, Li Yuehua, Zhu Hongbo, Wu Xiaoping, Mei Kai, Li Pian, Yang Qiao
The First Affiliated Hospital, Department of Medical Oncology, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
The First Affiliated Hospital, Department of Oncology Radiotherapy, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
J Oncol. 2022 Sep 17;2022:5456016. doi: 10.1155/2022/5456016. eCollection 2022.
Gastric cancer (GC) is one of the most prevalent malignancies in the digestive system across the world. The function and mechanism of PDLIM1, a cancer-suppressing gene, in gastric cancer progression remain unclear. This study is aimed at investigating the expression features and function of PDLIM1 in GC. RT-qPCR and western blot were used to compare the profiles of PDLIM1 and miR-187 between GC and normal tissues. The cell models of PDLIM1 overexpression and low expression were established in gastric cancer cell lines MKN45 and AGS. CCK8 and BrdU assays measured cell proliferation. Flow cytometry monitored cell apoptosis. Transwell analyzed cell invasion and migration. The influence of miR-187 overexpression on gastric cancer development was assessed. We predicted the targeted correlation between miR-187 and PDLIM1 through bioinformatics, which was corroborated via dual luciferase activity assay and RIP. Meanwhile, the cell model of PDLIM1 overexpression was built in AGS cells transfected with miR-187 mimics. A rescue experiment was conducted to assess the impact of PDLIM1 overexpression on the procancer function of miR-187. As a result, in contrast with normal paracancer tissues, PDLIM1 was substantially downregulated in GC tissues. Moreover, PDLIM1 overexpression considerably dampened proliferation, invasion, and migration in GC cells, boosted the cell apoptosis, and bolstered their sensitivity to cisplatin. PDLIM1 knockdown or miR-187 overexpression dramatically fostered GC cell proliferation, invasion, and migration and repressed cell apoptosis. Mechanism studies demonstrated that PDLIM1 vigorously restrained the profiles of the Hippo-YAP signaling pathway and the downstream target genes. miR-187 targeted PDLIM1, while miR-187 overexpression cramped PDLIM1 expression. The rescue experiment suggested that PDLIM1 overexpression weakened the procancer function of miR-187 in GC cells. In conclusion, our study demonstrated that PDLIM1 presented a low expression in GC tissues, while miR-187/PDLIM1 participated in GC development and cisplatin sensitivity by mediating the Hippo-YAP signaling pathway.
胃癌（GC）是全球消化系统中最常见的恶性肿瘤之一。抑癌基因PDLIM1在胃癌进展中的功能和机制仍不清楚。本研究旨在探讨PDLIM1在胃癌中的表达特征和功能。采用RT-qPCR和蛋白质免疫印迹法比较胃癌组织和正常组织中PDLIM1和miR-187的表达情况。在胃癌细胞系MKN45和AGS中建立了PDLIM1过表达和低表达的细胞模型。CCK8和BrdU检测法测定细胞增殖。流式细胞术监测细胞凋亡。Transwell法分析细胞侵袭和迁移。评估miR-187过表达对胃癌发展的影响。通过生物信息学预测miR-187与PDLIM1之间的靶向相关性，并通过双荧光素酶活性测定和RNA免疫沉淀法（RIP）进行验证。同时，在转染了miR-187模拟物的AGS细胞中建立了PDLIM1过表达的细胞模型。进行了挽救实验，以评估PDLIM1过表达对miR-187促癌功能的影响。结果显示，与正常癌旁组织相比，PDLIM1在胃癌组织中显著下调。此外，PDLIM1过表达显著抑制了胃癌细胞的增殖、侵袭和迁移，促进了细胞凋亡，并增强了其对顺铂的敏感性。敲低PDLIM1或过表达miR-187显著促进了胃癌细胞的增殖、侵袭和迁移，并抑制了细胞凋亡。机制研究表明，PDLIM1强烈抑制Hippo-YAP信号通路及其下游靶基因的表达。miR-18靶向PDLIM1，而过表达miR-187会抑制PDLIM1的表达。挽救实验表明，PDLIM1过表达减弱了miR-187在胃癌细胞中的促癌功能。总之，我们的研究表明，PDLIM1在胃癌组织中呈低表达，而miR-187/PDLIM1通过介导Hippo-YAP信号通路参与胃癌的发展和顺铂敏感性。
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