Abstract
BackgroundEmerging evidence has shown that miR-1275 plays a critical role in tumour metastasis and the progression of various types of cancer. In this study, we analysed the role and mechanism of miR-1275 in the progression and prognosis of gastric cancer (GC).MethodsTarget genes of miR-1275 were identified and verified by luciferase assay and Western blotting. The function of miR-1275 in invasion and metastasis was analysed in vitro and in vivo in nude mice. The signal pathway regulated by miR-1275 was examined by qRT-PCR, Western blotting and chromatin immunoprecipitation analyses. The expression of miR-1275and JAZF1 were measured in specimens of GC and adjacent non cancerous tissues.ResultsWe identified JAZF1 as a direct miR-1275 target. miR-1275 supresses migration and invasion of GC cells in vitro and in vivo, which was restored by JAZF1 overexpression. Moreover, JAZF1 was recognized as a direct regulator of Vimentin. Knocking-down miR-1275 or overexpressing JAZF1 resulted in upregulation of Vimentin but downregulation of E-cadherin. Meanwhile, we validated in 120 GC patients specimens that low miR-1275expression and high JAZF1 mRNA expression levels were closely associated with lymph node metastasis and poor prognosis. The expression of JAZF1 in protein level displayed the correlations with Vimentin but inversely with E-cadherin.ConclusionsIncreased miR-1275 expression inhibited GC metastasis by regulating vimentin/E-cadherin via direct suppression of JAZF1expression, suggesting that miR-1275 is a tumour-suppressor miRNA with the potential as a prognostic biomarker or therapeutic target in GC.
Highlights
Emerging evidence has shown that miR-1275 plays a critical role in tumour metastasis and the progression of various types of cancer
We demonstrated that miR-29c expression was frequently lower in gallbladder cancer (GBC) tissues than in adjacent nontumour tissues [15], indicating that miR-29c work as a potential tumour suppressor in GBC
We identified a mechanism that Juxtaposed with another zinc finger protein 1 (JAZF1) directly regulated the expression of vimentin and E-cadherin by bindinig to their promoter regions in gastric cancer (GC) cells
Summary
Emerging evidence has shown that miR-1275 plays a critical role in tumour metastasis and the progression of various types of cancer. We analysed the role and mechanism of miR-1275 in the progression and prognosis of gastric cancer (GC). Many novel targeted molecules and the underlying mechanisms related to tumour cell motility and metastasis have been reported, metastasis of tumour is still hard to be fully explained. Since the first miRNA was reported by Ambros and Ruvkun in 1993 [11], growing evidence has shown that miRNAs can function as either oncogenes or tumour suppressors in various cancers [12,13,14]. Much attention has been attracted by the critical function of miRNAs in metastasis, but it is still need to be revealed that the significance of the majority of miRNAs to GC and its pathological relevance
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