miR-598 acts as a tumor suppressor in human gastric cancer by targeting IGF-1R
Authors Liu N, Yang H, Wang H
Received 26 February 2018
Accepted for publication 29 March 2018
Published 17 May 2018 Volume 2018:11 Pages 2911—2923
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Dr Cho
Na Liu,1 Hua Yang,2 Hong Wang3
1Intensive Care Unit, Shandong Provincial Third Hospital, Shandong, China; 2Intensive Care Unit, Chiping County People’s Hospital, Shandong, China; 3Department of General Surgery, Shandong Provincial Third Hospital, Shandong, China
Background: In recent years, the aberrant expression of miR-598 in tumorigenesis has been demonstrated, as well as the fact that the IGF-1R pathway is also involved in the development of human gastric cancer (GC). The present study aimed to investigate the molecular mechanisms underlying miR-598-regulated IGF-1R expression in human GC.
Materials and methods: We analyzed the expression of miR-598 and IGF-1R in GC samples and cells, and evaluated the clinical significance of miR-598 and IGF-1R in GC patients. Furthermore, in vitro and in vivo assays were used to investigate the molecular mechanisms of miR-598 and IGF-1R.
Results: miR-598 expression was frequently downregulated in GC tissues and cells, and significantly correlated with poor prognosis, vascular invasion, TNM stage, and lymph node metastases as well as IGF-1R expression. The overexpression of miR-598 obviously inhibited cell proliferation, migration, invasion, and induced cell cycle arrest in the G1/S phase, and increased the apoptosis of GC cells. The overexpression of miR-598 also significantly inhibited ERK1/2 and Akt phosphorylation level. In vivo assay validated the inhibitory effect of miR-598 on tumor growth. Further studies showed that miR-598 inhibited IGF-1R protein expression by directly targeting its 3´-UTR. Besides, over-expression of IGF-1R reversed the inhibitory effects of miR-598, while suppression of IGF-1R expression showed inverse effects.
Conclusion: miR-598 suppresses GC cell proliferation, migration and invasion by directly targeting IGF-1R expression. Thus, miR-598 may be a useful target for GC patients.
Keywords: miR-598, IGF-1R, gastric cancer, proliferation, migration, invasion suppressor
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