miR-543 promotes gastric cancer cell proliferation by targeting SIRT1

Journal Article · Fri Jan 01 04:00:00 EST 2016 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.11.062· OSTI ID:22594154

Li, Juan; Dong, Guoying ^[1]; Wang, Bo ^[2]; Gao, Wei ^[3]; Yang, Qing ^[1]

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1. Institute of Pathogen Biology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan 250012 (China)
2. Department of Traditional Chinese Medicine, Qilu Hospital, Shandong University, Jinan 250012 (China)
3. Department of Pathology, Jinan Central Hospital, Jinan 250013 (China)

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. - Highlights: • SIRT1 is a novel target of miR-543. • miR-543 promotes gastric cancer cell proliferation and cell cycle progression by targeting SIRT1. • miR-543 is upregulated in GC and positively associated with tumor size, clinical grade, TNM stage and lymph node metastasis. • miR-543 is negatively correlated with SIRT1 expression in gastric cancer tissues.

• OSTI ID: 22594154
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 469; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL CYCLE
CELL PROLIFERATION
EPITHELIUM
GENE REGULATION
HISTONES
LYMPH
LYMPH NODES
METASTASES
NEOPLASMS
POLYMERASE CHAIN REACTION