title: MiR-199a-3p promotes gastric cancer progression by targeting ZHX1.
abstract: Accumulating evidence has indicated that microRNAs (miRNAs) act as critical epigenetic regulators in tumor carcinogenesis. Here, we report that miR-199a-3p was significantly upregulated in gastric cancer (GC) cell lines and tissues. Functional studies demonstrated that miR-199a-3p dramatically increased cell proliferation and suppressed cell apoptosis both in vitro and in vivo. Furthermore, the transcriptional regulator zinc fingers and homeoboxes 1 (ZHX1) was identified as one of the direct downstream targets of miR-199a-3p, miR-199a-3p bound to the ZHX1 3′ untranslated region (3′UTR) to regulate ZHX1 protein expression. In addition, the expression of miR-199a-3p was inversely associated with that of ZHX1 in GC cell lines. Overexpression of miR-199a-3p in SGC-7901 cells inhibited ZHX1 expression, while reduction in miR-199a-3p by inhibitors in NCI-N87 cells enhanced ZHX1 expression. Moreover, restoring ZHX1 expression in SGC-7901/miR-199a-3p cells inhibited the cell proliferation induced by miR-199a-3p. Taken together, these findings suggest that miR-199a-3p may function as a novel tumor promoter in GC and its oncogenic activity may involve the direct targeting and inhibition of ZHX1.
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Xingjie
authors.initials: X
authors.lastname: Ma
authors.forename: Qiang
authors.initials: Q
authors.lastname: Cai
authors.forename: Xinjing
authors.initials: X
authors.lastname: Wang
authors.forename: Beiqin
authors.initials: B
authors.lastname: Yu
authors.forename: Qu
authors.initials: Q
authors.lastname: Cai
authors.forename: Bingya
authors.initials: B
authors.lastname: liu
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Zhu
authors.forename: Chen
authors.initials: C
authors.lastname: Li
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D014157:Transcription Factors / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; D035683:MicroRNAs; D014157:Transcription Factors; C484404:ZHX1 protein, human; C531408:mirn199 microRNA, human