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

被引:31
|
作者
Mei, Jia-Wei [1 ,2 ,3 ,4 ]
Yang, Zi-Yi [1 ,2 ,3 ,4 ]
Xiang, Hong-Gang [5 ]
Bao, Runfa [1 ,2 ,3 ,4 ]
Ye, Yuan-Yuan [1 ,2 ,3 ,4 ]
Ren, Tai [1 ,2 ,3 ,4 ]
Wang, Xue-Feng [1 ,2 ,3 ,4 ]
Shu, Yi-Jun [1 ,2 ,3 ,4 ]
机构
[1] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Dept Gen Surg, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
[2] Shanghai Jiao Tong Univ, Xinhua Hosp, Sch Med, Lab Gen Surg, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
[3] Shanghai Key Lab Biliary Tract Dis Res, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
[4] Shanghai Jiao Tong Univ, Sch Med, Inst Biliary Tract Dis, 1665 Kongjiang Rd, Shanghai 200092, Peoples R China
[5] Shanghai Univ Med & Hlth Sci, Peoples Hosp, Pudong New Area, Dept Gen Surg, 490 South Chuanhuan Rd, Shanghai 201299, Peoples R China
基金
中国国家自然科学基金;
关键词
Gastric cancer; miR-1275; JAZF1; Tumour progression; RNA interference; METASTASIS; PROLIFERATION; MIR-1275; CARCINOMA; GENES; PROGRESSION; EXPRESSION; SYNBINDIN; TARGETS; FUSION;
D O I
10.1186/s12885-019-5929-1
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页数:12
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