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.
Shanghai Key Laboratory of Biliary Tract Disease Research, No. 1665 Kongjiang Road, Shanghai, 200092, China.
BMC Cancer. 2019 Jul 29;19(1):740. doi: 10.1186/s12885-019-5929-1.
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).
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.
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.
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.
新出现的证据表明，miR-1275 在肿瘤转移和各种类型癌症的进展中发挥着关键作用。在这项研究中，我们分析了 miR-1275 在胃癌（GC）进展和预后中的作用和机制。
通过荧光素酶报告基因实验和 Western blot 验证 miR-1275 的靶基因。在体外和裸鼠体内分析 miR-1275 在侵袭和转移中的功能。通过 qRT-PCR、Western blot 和染色质免疫沉淀分析检测受 miR-1275 调控的信号通路。检测 GC 标本和相邻非癌组织中 miR-1275 和 JAZF1 的表达。
我们确定 JAZF1 是 miR-1275 的直接靶基因。miR-1275 抑制 GC 细胞在体外和体内的迁移和侵袭，而 JAZF1 的过表达则恢复了这一作用。此外，JAZF1 被认为是 Vimentin 的直接调节因子。敲低 miR-1275 或过表达 JAZF1 导致 Vimentin 上调，而 E-cadherin 下调。同时，我们在 120 例 GC 患者标本中验证到，miR-1275 表达降低和 JAZF1 mRNA 表达水平升高与淋巴结转移和预后不良密切相关。JAZF1 蛋白水平的表达与 Vimentin 呈正相关，与 E-cadherin 呈负相关。
miR-1275 表达增加通过直接抑制 JAZF1 的表达来调节 vimentin/E-cadherin，从而抑制 GC 转移，表明 miR-1275 是一种肿瘤抑制 miRNA，具有作为 GC 预后生物标志物或治疗靶点的潜力。
