Precision Medicine Center, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China; Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
Jiangsu Breast Disease Center, The First Affliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
Exp Cell Res. 2021 Sep 1;406(1):112741. doi: 10.1016/j.yexcr.2021.112741. Epub 2021 Jul 21.
BACKGROUND: RNPC1 is reported to act as a tumor suppressor by binding and regulating the expression of target genes in various cancers. However, the role of RNPC1 in gastric cancer and the underlying mechanisms are still unclear. METHODS: Gastric cancer cells were stably transfected with lentivirus. Proliferation, migration, invasion, cell cycle in vitro and tumorigenesis in vivo were used to assess the role of RNPC1. Quantitative real-time PCR, western blotting and immunohistochemistry were used to detect the relationship between RNPC1 and aurora kinase B (AURKB). RNA immunoprecipitation (RIP), RNA electrophoretic mobility shift assays (REMSAs), and dual-luciferase reporter assays were used to identify the direct binding sites of RNPC1 with AURKB mRNA. A CCK-8 assay was conducted to confirm the function of AURKB in RNPC1-induced growth promotion. RESULTS: High RNPC1 expression was found in gastric cancer tissues and cell lines and was associated with high TNM stage. RNPC1 overexpression significantly promoted the proliferation, migration, and invasion of gastric cancer cells. Knockdown of RNPC1 could impede gastric cancer tumorigenesis in nude mice. AURKB expression was positively related to RNPC1. RNPC1 directly binds to the 3'-untranslated region (3'-UTR) of AURKB and enhances AURKB mRNA stability. AURKB reversed the proliferation induced by RNPC1 in gastric cancer cells. RNPC1 resulted in mitotic defects, aneuploidy and chromosomal instability in gastric cancer cells, similar to AURKB. CONCLUSION: RNPC1 acts as an oncogene in gastric cancer by influencing cell mitosis by increasing AURKB mRNA stability, which may provide a potential biomarker and a therapeutic target for gastric cancer.
背景：RNPC1 被报道在多种癌症中作为肿瘤抑制因子通过结合和调节靶基因的表达来发挥作用。然而，RNPC1 在胃癌中的作用及其潜在机制仍不清楚。
方法：通过慢病毒稳定转染胃癌细胞。体外评估 RNPC1 对细胞增殖、迁移和侵袭、细胞周期的影响以及体内评估其致瘤性。实时定量 PCR、Western blot 和免疫组织化学检测 RNPC1 与 Aurora 激酶 B（AURKB）之间的关系。RNA 免疫沉淀（RIP）、RNA 电泳迁移率变动分析（REMSAs）和双荧光素酶报告基因检测鉴定 RNPC1 与 AURKB mRNA 的直接结合位点。CCK-8 实验验证 AURKB 在 RNPC1 诱导的生长促进中的作用。
结果：在胃癌组织和细胞系中发现高表达的 RNPC1，且与高 TNM 分期相关。RNPC1 过表达显著促进胃癌细胞的增殖、迁移和侵袭。RNPC1 敲低可抑制裸鼠胃癌肿瘤的发生。AURKB 的表达与 RNPC1 呈正相关。RNPC1 直接结合 AURKB 的 3'非翻译区（3'-UTR）并增强 AURKB mRNA 的稳定性。AURKB 逆转了 RNPC1 在胃癌细胞中引起的增殖。RNPC1 导致胃癌细胞有丝分裂缺陷、非整倍体和染色体不稳定性，类似于 AURKB。
结论：RNPC1 通过增加 AURKB mRNA 的稳定性影响细胞有丝分裂，从而在胃癌中发挥癌基因作用，这可能为胃癌提供潜在的生物标志物和治疗靶点。
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