MiR-129-5p Induces Cell Cycle Arrest Through Modulating HOXC10/Cyclin D1 to Inhibit Gastric Cancer Progression

Background: MicroRNAs (miRNAs) play important roles in post-transcriptional regulation and may serve as targets for the diagnosis and treatment of cancers. Nevertheless, a comprehensive understanding of miRNAs profiles in gastric cancer (GC) progression is still lacking. Methods: Bioinformatics analyses, qRT-PCR, western blotting, and immunohistochemistry were applied for detecting miR-129-5p, HOXC10 and Cyclin D1 expression in GC tissues. Kaplan-Meier analysis with log-rank test was used for survival analyses. ChIP assay was performed for identifying potential gene regulated by HOXC10. Series in vitro and in vivo assays were used for exploring the function of miR-129-5p, HOXC10 and Cyclin D1 in the progression of GC. Findings: MiR-129-5p is downregulated in gastric cancer tissues and inhibits gastric cancer proliferation by inducing cycle cell arrest. MiR-129-5p directly targeted the 3’ untranslated regions (3’ UTR) of HOXC10 mRNA and downregulated its expression. Importantly, miR-129-5p could reverse the oncogenic effect induced by HOXC10. We systemically screened the downstream target of HOXC10 by ChIP-sequencing, and found that HOXC10 could transcriptionally regulate the expression of Cyclin D1 and facilitate G1/S cell cycle transition. Interpretation: MiR-129-5p/HOXC10/Cyclin D1 axis modulates cell cycle and gastric tumorigenesis, which might provide potential prognostic biomarkers and therapeutic targets for gastric cancer patients. Funding Statement: This work was supported by National Natural Science Foundation of China (31771540, 81802348, 81972276); Natural Science Foundation of Zhejiang Province (LY18H160011, LYY19H310011); Fundamental Research Funds for the Central Universities (2017QNA7005); Zhejiang Provincial Medical and Health Science and Technology Project (2018KY464). Declaration of Interests: The authors declare no potential conflicts of interest. Ethical Approval Statement: Animal experimental protocols were approved by the Committee of Animal Ethics of Zhejiang University. Informed written consent was obtained from all participants, and the study was approved by the ethics committee of Sir Run Run Shaw Hospital and The First Affiliated Hospital in Zhejiang University.