574436

MIR485

MicroRNA (miRNA or miR)485 is a functional miRNA which has received much attention in recent years. However, little is known about the expression of miR485 or the role it plays in bladder cancer [namely in metastasis and epithelialmesenchymal transition (EMT)]. Thus, in the present study, we aimed to detect the expression of miR485 in human bladder cancer tissues and bladder cancer cell lines, and to examine the effects of miR4855p on bladder cancer cell metastasis and EMT. We found that the expression of miR4855p was downregulated in the human bladder cancer tissues and different bladder cancer cell lines compared with the normal tissues and cell lines, as demonstrated by reverse transcriptionquantitative polymerase chain reaction (RTqPCR). We enforced the expression of miR4855p in T24 cells and inhibited the expression of miR4855p in SW780 cells by transfection with miR4855p mimic or miR4855p inhibitor, respectively. The ectopic expression of miR4855p was shown to inhibit cell metastasis and EMT, whereas the inhibition of miR4855p expression promoted cell metastasis and EMT, as shown by transwellmatrigel assay, cell adhesion assay and western blot analysis. Furthermore, a luciferase reporter assay revealed that high mobility group AThook 2 (HMGA2) was a direct target of miR4855p and that the overexpression of HMGA2 reversed the effects of miR4855p on cell metastasis and EMT. In conclusion and to the very best of our knowledge, the present study, for the first time, identified miR4855p as a suppressive miRNA in human bladder cancer, and demonstrated that miR4855p inhibits cell metastasis and EMT at least partly through the suppression of HMGA2 expression.

Lung adenocarcinoma, as a common form of non-small cell lung cancer, poses a significant threat to public health worldwide. Previous studies have reported that flotillin-2 (Flot2) is often overexpressed in various tumors and is h correlated with tumor progression and patient survival. Dysregulated microRNA (miRNA) is associated with various cancers, including lung adenocarcinoma. However, little is known about the miRNAs targeting Flot2 in lung adenocarcinoma. In this study, we found that the expression level of miR-485 was downregulated in four lung adenocarcinoma cell lines and tissues and that the reduced miR-485 expression was associated with tumor metastasis. Luciferase assay revealed that Flot2 is direct target of miR-485, while the expression levels of Flot2 were inversely correlated with the expression levels of miR-485 in lung adenocarcinoma tissues. Ectopic Flot2 could significantly reverse miR-485-mediated inhibition of metastasis and EMT, demonstrating Flot2 downregulation is involved in function of miR-485. Subsequently, we found that miR-485 suppressed the activity of PI3K/AKT/mTOR signaling in lung adenocarcinoma cells. In conclusion, the present study provided novel insight into the molecular mechanism of lung adenocarcinoma progression and demonstrating miR-485 as a potential therapeutic target in human lung adenocarcinoma.CI - Copyright (c) 2016. Published by Elsevier Inc.

Oral squamous cell carcinoma (OSCC) is currently a highly prevalent disease worldwide. Cisplatin (CDDP) is widely used for the chemotherapy of OSCC. Yet, the molecular mechanisms responsible for cisplatin resistance have not been fully elucidated. In this study, we showed that overexpression of p21 (RAC1) activated kinase 1 (PAK1) induced epithelial to mesenchymal transition (EMT) and significantly promoted the invasion and migration of oral squamous cell carcinoma SCC25 cells. Emerging evidence indicates a strong link between resistance to therapy and the induction of EMT in cancer. We showed that overexpression of PAK1 induced cisplatin resistance in SCC25 cells. ERCC1 and YAP can promote cisplatin resistance in human OSCC. We showed that ERCC1 and YAP protein were upregulated by PAK1 in SCC25 cells. -We found that miR4855p inhibited PAK1 protein expression in the SCC25 cells. Contrary to PAK1, we demonstrated that overexpression of miR4855p reversed EMT and significantly inhibited invasion and migration. Moreover, its overexpression sensitized SCC25-CR cells (cisplatin-resistant cells) to cisplatin. Thus, we conclude that miR4855p reverses EMT and promotes cisplatin-induced cell death by targeting PAK1 in oral tongue squamous cell carcinoma. This study suggests that PAK1 plays an essential role in the progression of OSCC and it is a potential therapeutic target for OSCC.