title: The role of microRNA-1274a in the tumorigenesis of gastric cancer: accelerating cancer cell proliferation and migration via directly targeting FOXO4.
abstract: MicroRNAs (miRNAs) are a series of 18-25 nucleotides length non-coding RNAs, which play critical roles in tumorigenesis. Previous study has shown that microRNA-1274a (miR-1274a) is upregulated in human gastric cancer. However, its role in gastric cancer progression remains poorly understood. Therefore, the current study was aimed to examine the effect of miR-1274a on gastric cancer cells. We found that miR-1274a was overexpressed in gastric cancer tissues or gastric cancer cells including HGC27, MGC803, AGS, and SGC-7901 by qRT-PCR analysis. Transfection of miR-1274a markedly promoted gastric cancer cells proliferation and migration as well as induced epithelial-mesenchymal transition (EMT) of cancer cells. Our further examination identified FOXO4 as a target of miR-1274a, which did not influence FOXO4 mRNA expression but significantly inhibited FOXO4 protein expression. Moreover, miR-1274a overexpression activated PI3K/Akt signaling and upregulated cyclin D1, MMP-2 and MMP-9 expressions. With tumor xenografts in mice models, we also showed that miR-1274a promoted tumorigenesis of gastric cancer in vivo. In all, our study demonstrated that miR-1274a prompted gastric cancer cells growth and migration through dampening FOXO4 expression thus provided a potential target for human gastric cancer therapy.
authors.affiliation: The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. Electronic address: wwangguojun@163.com.
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Guang-Hui
authors.initials: GH
authors.lastname: Liu
authors.affiliation: The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Ye
authors.affiliation: The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fu
authors.affiliation: The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
authors.forename: Xie-Fu
authors.initials: XF
authors.lastname: Zhang
mesh_terms: D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009362:Neoplasm Metastasis; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C108803:FOXO4 protein, human; D051858:Forkhead Transcription Factors; C000598351:MIRN1274 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors
keywords: Epithelial–mesenchymal transition; FOXO4; Gastric cancer; MicroRNA-1274a; Migration; Proliferation