2. Academic Validation
  3. RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing aurora kinase B mRNA

RNA-binding protein RNPC1 acts as an oncogene in gastric cancer by stabilizing aurora kinase B mRNA

  • Exp Cell Res. 2021 Sep 1;406(1):112741. doi: 10.1016/j.yexcr.2021.112741.
Chun-Mei Ji 1,  Xu Zhang 2,  Wentong Fang 3,  Ling Meng 3,  Xiaolong Wei 4,  Chen Lu 5
Affiliations

Affiliations

  • 1 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.
  • 2 Jiangsu Breast Disease Center, The First Affliated Hospital with Nanjing Medical University, Nanjing City, Jiangsu Province, 210000, China.
  • 3 Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
  • 4 Department of Pathology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, 515041, China. Electronic address: [email protected].
  • 5 Precision Medicine Center, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, China. Electronic address: [email protected].
PMID: 34302858 DOI: 10.1016/j.yexcr.2021.112741
Abstract

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.

Keywords

Aurora kinase B; Gastric cancer; Oncogene; RNPC1; mRNA stability.

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