MiR-129-5p induces cell cycle arrest through modulating HOXC10/Cyclin D1 to inhibit gastric cancer progression

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作者：Jiamin He, Qiwei Ge, Zhenghua Lin, Weiyi Shen, Renbin Lin, Jiaguo Wu, Boya Wang, Yunkun Lu, Luyi Chen, Xiaosun Liu, Wenfang Zheng, Ying Zhang, Lan Wang, Kan Wang, Liangjing Wang, Wei Zhuo, Shujie Chen
期刊：FASEB JOURNAL
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MicroRNAs (miRNAs) play important roles in posttranscriptional regulation and may serve as targets for the diagnosis and treatment of cancers. Nevertheless, a comprehensive understanding of miRNAs profiles in gastric cancer progression is still lacking. Here, we report that miR-129-5p is downregulated in gastric cancer by analyzing TCGA database (n = 41) and clinical tumor samples (n = 60). MiR-129-5p transfection suppressed gastric cancer cell proliferation through inducing G1 phase arrest in vitro and inhibit xenograft tumor growth in vivo. 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. Notably, high levels of HOXC10 and Cyclin D1 were related with poor prognosis of gastric cancer patients (n = 90). These findings reveal a novel role of miR-129-5p/HOXC10/Cyclin D1 axis in modulating cell cycle and gastric tumorigenesis, which might provide potential prognostic biomarkers and therapeutic targets for gastric cancer patients.