title: MicroRNA-410 suppresses migration and invasion by targeting MDM2 in gastric cancer.
abstract: Gastric cancer is one of the most frequent malignancies in tumors in the East Asian countries. Identifying precise prognostic markers and effective therapeutic targets is important in the treatment of gastric cancer. microRNAs (miRNAs) play important roles in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In this study, we found that the levels of miR-410 in gastric cancer and cell lines were much lower than that in the normal control, respectively, and the lower level of miR-410 was significantly associated with lymph-node metastasis. Transfection of miR-410 mimics could significantly inhibit the cell proliferation, migration and invasion in the HGC-27 gastric cancer cell lines. In contrast, knockdown of miR-410 had the opposite effect on the cell proliferation, migration and invasion. Moreover, we also found that MDM2 was negatively regulated by miR-410 at the post-transcriptional level, via a specific target site with the 3'UTR by luciferase reporter assay. The expression of MDM2 was inversely correlated with miR-410 expression in gastric cancer tissues, and overexpression of MDM2 in miR-410-transfected gastric cancer cells effectively rescued the inhibition of cell proliferation and invasion caused by miR-410. Thus, our findings suggested that miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting gastric cancer cells proliferation, migration and invasion. The findings of this study contributed to the current understanding of these functions of miR-410 in gastric cancer.
authors.affiliation: Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Shen
authors.affiliation: Oncology Department, Anhui Cancer Hospital, Hefei, China.
authors.forename: Weina
authors.initials: W
authors.lastname: Niu
authors.affiliation: Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Anhui Provincial Hospital, Hefei, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C568527:MIRN410 microRNA, human; D035683:MicroRNAs; D008156:Luciferases; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2