100302203

MIR1271

BACKGROUND/AIMS: FOXQ1 overexpression has been reported to enhance tumor growth and invasion. However, the biological function of FOXQ1 and the mechanism underlying its upregulation in gastric cancer (GC) remain unknown. METHODS: QPCR was used to detect the expression of miR-1271 and FOXQ1 in specimens from GC patients. FOXQ1-siRNA, and miR- 1271 mimics and inhibitor were transfected into human MGC-803 and SGC-7901 cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. Markers of epithelial-mesenchymal transition (EMT) were detected by western blot analysis. RESULTS: MiR-1271 was downregulated in both GC tissues and GC cell lines. The expression of miR-1271 was inversely correlated with tumor size (P = 0.017), tumor stage (P = 0.035), lymph node metastasis (P = 0.018), and TNM stage (P = 0.025). Ectopic expression of miR-1271 dramatically suppressed GC cell proliferation, invasion, and EMT. Furthermore, FOXQ1 was identified as a direct target of miR-1271. Knockdown of FOXQ1 inhibited GC cell malignant behavior, whereas FOXQ1 overexpression partially restored the suppression effects of miR-1271. Additionally, miR-1271 expression was negatively correlated with FOXQ1 in GC tissues. CONCLUSIONS: MiR-1271 inhibits cell proliferation, invasion, and EMT in GC by directly suppressing FOXQ1 expression.CI - (c) 2015 S. Karger AG, Basel.

Pancreatic cancer (PC) remains one of the most lethal types of cancer in adults. The purpose of this study was to determine the role of miR-1271 in regulation of epithelial mesenchymal transition (EMT) and metastasis of pancreatic cancer cells. miR-1271 was identified to be significantly down-regulated in PC tissues by miRNA array. Also, an increase of EMT-regulators ZEB1 and TWIST1 expression level is accompanied by a decrease of miR-1271. We showed that expression of miR-1271 was significantly down-regulated in PC tissues as compared with that in normal tissues. In addition, our results showed that miR-1271 expression levels were decreased while ZEB1 and TWIST1 expression levels were increased in detected PC cell lines. Moreover, ectopic expression of miR-1271 suppressed and antagomiR-1271 promoted proliferation, migration, and invasion in SW1990 and PANC-1 cells. Bioinformatics coupled with luciferase and Western blot assays also revealed that miR-1271 inhibited expression of ZEB1 and TWIST1, which are master regulators of tumor metastasis. Our study first indicates that miR-1271 functions as a suppressor in regulating of pancreatic cancer EMT by targeting ZEB1 and TWIST1, and it promise as a therapeutic target and prognostic marker for metastatic pancreatic cancer.CI - Copyright (c) 2016 Elsevier Inc. All rights reserved.

MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma (HCC) metastasis. In the present study, we focused on the functions of miR-1271 in HCC metastasis. The downregulation of miR-1271 was found to be associated with to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented HCC cell migration and invasion, as well as the formation of lung metastatic clusters. In addition, miR-1271 was demonstrated to markedly inhibit the epithelial-mesenchymal transition (EMT) of HCC cells. Importantly, protein tyrosine phosphatase type IVA member 1 (PTP4A1) was identified as a direct downstream target of miR-1271 in HCC. Furthermore, we confirmed that the phosphorylation of c-Src at Tyr416 mediated by PTP4A1 was a potential anti-HCC mechanism of action of miR-1271. On the whole, our data indicate that miR-1271 inhibits HCC metastasis by targeting the PTP4A1/c-Src signaling pathway and may serve as a prospective cancer therapeutic target for HCC.