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MiR‐129‐5p induces cell cycle arrest through modulating HOXC10/Cyclin D1 to inhibit gastric cancer progression
Author(s) -
He Jiamin,
Ge Qiwei,
Lin Zhenghua,
Shen Weiyi,
Lin Renbin,
Wu Jiaguo,
Wang Boya,
Lu Yunkun,
Chen Luyi,
Liu Xiaosun,
Zheng Wenfang,
Zhang Ying,
Wang Lan,
Wang Kan,
Wang Liangjing,
Zhuo Wei,
Chen Shujie
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201903217r
Subject(s) - cyclin d1 , cancer , microrna , cancer research , cell cycle , carcinogenesis , cancer cell , biology , untranslated region , cell growth , gene , messenger rna , genetics
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.