title: microRNA-148a suppresses human gastric cancer cell metastasis by reversing epithelial-to-mesenchymal transition.
abstract: MicroRNAs (miRNAs) are important regulators of gastric cancer development and progression. miR-148a is one of the most frequently and highly downregulated miRNAs in gastric cancer and is associated with advanced clinical stage and poor prognosis. In this study, we investigated the role of miR-148a in gastric cancer metastasis. Levels of miR-148a were determined by qRT-PCR in 60 gastric cancer samples. Cell migration and invasion assays were performed in a stably expressing miRNA-148a gastric cancer cell line established using a lentivirus expression system. Epithelial-mesenchymal transition (EMT) was evaluated using qRT-PCR and Western Blots to detect epithelial marker E-cadherin and mesenchymal marker, vimentin. Luciferase reporter assays were used to identify downstream targets and biological function of miR-148a. Gastric cancer tissue had significantly lower expression of miR-148a compared to non-tumor tissue. Low miR-148a levels were associated with lymph node metastasis, N stage, and blood vessel invasion. miR-148a overexpression inhibited metastasis of gastric cancer cells. miR-148a overexpression also downregulated vimentin expression and upregulated E-cadherin expression, suggesting that miR-148a inhibited EMT. Finally, the SMAD2 gene was identified as the direct and functional target of miR-148a. MiR-148a suppresses gastric cancer metastasis and EMT, likely via SMAD2. Restoration of miR-148a expression could have important implications in gastric cancer therapy.
authors.affiliation: Department of General Surgery, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, No. 650 Xinsongjiang Road, Songjiang District, Shanghai, 200080, People's Republic of China.
authors.forename: Sui-Han
authors.initials: SH
authors.lastname: Wang
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Zhou
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Cao
authors.forename: Chao
authors.initials: C
authors.lastname: Shi
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Zhou
authors.forename: Yu-Gang
authors.initials: YG
authors.lastname: Wen
authors.forename: Yang
authors.initials: Y
authors.lastname: Shen
authors.forename: Ji-Kun
authors.initials: JK
authors.lastname: Li
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051899:Smad2 Protein / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism
chemical_list: D015820:Cadherins; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D014746:Vimentin