RUNX3 regulates vimentin expression via miR-30a during epithelial-mesenchymal transition in gastric cancer cells.
Runt-related transcription factor 3 (RUNX3) is a putative tumour suppressor via regulating the expression of a series of target genes. Clinical studies demonstrated that loss of RUNX3 expression is associated with gastric cancer progression and poor prognosis, but the underlying mechanism is not entirely clear. Accumulating evidence shows that the epithelial-mesenchymal transition (EMT) plays an important role in cancer relapse and metastasis. Therefore, we addressed whether RUNX3 has a role in the EMT in gastric cancer. Knockdown of RUNX3 promoted cell invasion and increased the protein expression of the mesenchymal marker vimentin in human gastric cancer cells. Overexpression of RUNX3 suppressed cell invasion and decreased the protein expression of vimentin in the cells and inhibited gastric cancer cells colonization in nude mice. Furthermore, overexpression of RUNX3 increased the expression of microRNA-30a (miR-30a), and miR-30a directly targeted the 3' untranslated region of vimentin and decreased its protein level. miR-30a inhibitor abrogated RUNX3-mediated inhibition of cell invasion and downregulation of vimentin. Thus, RUNX3 suppressed gastric cancer cell invasion and vimentin expression by activating miR-30a. In gastric cancer patients, levels of RUNX3 were positively correlated with miR-30a and negatively associated with the levels of vimentin. Collectively, our data suggest a novel molecular mechanism for the tumour suppressor activity of RUNX3. Effective therapy targeting the RUNX3 pathway may help control gastric cancer cell invasion and metastasis by inhibiting the EMT.
Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, China.
Zhifang
Z
Liu
Long
L
Chen
Xinchao
X
Zhang
Xia
X
Xu
Huaixin
H
Xing
Yingjie
Y
Zhang
Wenjuan
W
Li
Han
H
Yu
Jiping
J
Zeng
Jihui
J
Jia
D000818:Animals; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D014746:Vimentin / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays
D050677:Core Binding Factor Alpha 3 Subunit; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C493729:Runx3 protein, human; D014746:Vimentin
Gastric cancer; Runt-related transcription factor 3; epithelial-mesenchymal transition; miR-30a; vimentin