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BMC Cancer. 2019 Jul 29;19(1):740. doi: 10.1186/s12885-019-5929-1.

MicroRNA-1275 inhibits cell migration and invasion in gastric cancer by regulating vimentin and E-cadherin via JAZF1.

Mei JW1,2,3, Yang ZY1,2,3, Xiang HG4, Bao R1,2,3, Ye YY1,2,3, Ren T1,2,3, Wang XF5,6,7, Shu YJ8,9,10.

Author information

1
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, China.
2
Shanghai Key Laboratory of Biliary Tract Disease Research, No. 1665 Kongjiang Road, Shanghai, 200092, China.
3
Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, China.
4
Department of General Surgery, Pudong New Area People's Hospital affiliated to Shanghai University of Medicine and Health Science, No. 490, South Chuanhuan Road, Pudong New Area, Shanghai, 201299, China.
5
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, China. wxxfd@live.cn.
6
Shanghai Key Laboratory of Biliary Tract Disease Research, No. 1665 Kongjiang Road, Shanghai, 200092, China. wxxfd@live.cn.
7
Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, China. wxxfd@live.cn.
8
Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital, Affiliated with Shanghai Jiao Tong University, School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, China. shuyijun@xinhuamed.com.cn.
9
Shanghai Key Laboratory of Biliary Tract Disease Research, No. 1665 Kongjiang Road, Shanghai, 200092, China. shuyijun@xinhuamed.com.cn.
10
Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, No. 1665 Kongjiang Road, Shanghai, 200092, China. shuyijun@xinhuamed.com.cn.

Abstract

BACKGROUND:

Emerging 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).

METHODS:

Target 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.

RESULTS:

We 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.

CONCLUSIONS:

Increased 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.

KEYWORDS:

Gastric cancer; JAZF1; RNA interference; Tumour progression; miR-1275

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