title: MicroRNA-149 inhibits proliferation and cell cycle progression through the targeting of ZBTB2 in human gastric cancer.
abstract: An increasing body of evidence indicates that miR-149 can both suppress and promote tumor growth depending on the tumor type. However, the role of miR-149 in the progression of gastric cancer (GC) remains unknown. Here we report that miR-149 is a tumor suppressor in human gastric cancer. miR-149 expression is decreased in GC cell lines and clinical specimens in comparison to normal gastric epithelial cell and tissues, respectively. The expression levels of miR-149 also correlate with the differentiation degree of GC cells and tissues. Moreover, ectopic expression of miR-149 in gastric cancer cells inhibits proliferation and cell cycle progression by down-regulating ZBTB2, a potent repressor of the ARF-HDM2-p53-p21 pathway, with a potential binding site for miR-149 in its mRNA's 3'UTR. It is also found that ZBTB2 expression increases in GC cells and tissues compared to normal gastric epithelial cell and tissues, respectively. Silencing of ZBTB2 leads to suppression of cell growth and cell cycle arrest in G0/G1 phase, indicating that ZBTB2 may act as an oncogene in GC. Furthermore, transfection of miR-149 mimics into gastric cancer cells induces down-regulation of ZBTB2 and HDM2, and up-regulation of ARF, p53, and p21 compared to the controls. In summary, our data suggest that miR-149 functions as a tumor suppressor in human gastric cancer by, at least partially through, targeting ZBTB2.
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi'an, Shaanxi, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiushan
authors.initials: X
authors.lastname: Zheng
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhou
authors.forename: Guohong
authors.initials: G
authors.lastname: Zhao
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yang
authors.forename: Limin
authors.initials: L
authors.lastname: Xia
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Cai
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Cailin
authors.initials: C
authors.lastname: Zhu
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Dexin
authors.initials: D
authors.lastname: Zhang
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D016193:G1 Phase / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; C551557:MIRN149 microRNA, human; D035683:MicroRNAs; D012097:Repressor Proteins; C544396:ZBTB2 protein, human