title: miR-543 promotes gastric cancer cell proliferation by targeting SIRT1.
abstract: SIRT1, a class III histone deacetylase, exerts inhibitory effects on tumorigenesis and is downregulated in gastric cancer. However, the role of microRNAs in the regulation of SIRT1 in gastric cancer is still largely unknown. Here, we identified miR-543 as a predicted upstream regulator of SIRT1 using 3 different bioinformatics databases. Mimics of miR-543 significantly inhibited the expression of SIRT1, whereas an inhibitor of miR-543 increased SIRT1 expression. MiR-543 directly targeted the 3'-UTR of SIRT1, and both of the two binding sites contributed to the inhibitory effects. In gastric epithelium-derived cell lines, miR-543 promoted cell proliferation and cell cycle progression, and overexpression of SIRT1 rescued the above effects of miR-543. The inhibitory effects of miR-543 on SIRT1 were also validated using clinical gastric cancer samples. Moreover, we found that miR-543 expression was positively associated with tumor size, clinical grade, TNM stage and lymph node metastasis in gastric cancer patients. Our results identify a new regulatory mechanism of miR-543 on SIRT1 expression in gastric cancer, and raise the possibility that the miR-543/SIRT1 pathway may serve as a potential target for the treatment of gastric cancer.
authors.affiliation: Institute of Pathogen Biology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Pathogen Biology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Dong
authors.affiliation: Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Pathology, Jinan Central Hospital, Jinan 250013, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Institute of Pathogen Biology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012, China. Electronic address: yangqing07@sdu.edu.cn.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D048429:Cell Size; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics*; D060787:Neoplasm Grading; D011485:Protein Binding; D056564:Sirtuin 1 / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: C577592:MIRN543 microRNA, human; D035683:MicroRNAs; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Gastric cancer; Proliferation; SIRT1; miR-543