Παρασκευή 7 Απριλίου 2017

Clinicopathological significance of miR-146a/WASF2 axis in gastric cancer

Abstract

Gastric cancer (GC) is one of the most common malignancies, and cancer invasion and metastasis are the leading causes of cancer-induced death in GC patients. WASF2 (WASP-family verprolin-homologous protein-2), with a role controlling actin polymerization which is critical in the formation of membrane protrusions involved in cell migration and invasion, has been demonstrated to possess cancer-promoting effects in several cancers. However, Data of WASF2′s role in GC is relatively few and even contradictory. In this study, we analyzed WASF2's expression in GC tissues and their corresponding adjacent normal tissues. We found that WASF2 was up-regulated in GC tissues and high level of WASF2 was associated with lymph node metastasis of GC. Through gain- and loss-of-function studies, WASF2 was demonstrated to significantly increase GC cells migration and invasion, but had no effect on proliferation in vitro. Importantly, WASF2 was also found to enhance GC metastasis in vivo. Our previous research suggested that WASF2 was a direct target of miR-146a. Furthermore, we analysed miR-146a's level in GC tissues and their corresponding adjacent normal tissues. We found that miR-146a was down-regulated in GC tissues and low miR-146a level was associated with advanced tumor-node-metastasis (TNM) stage and lymph node metastasis. Its' level in GC tissues were negatively correlated with WASF2 expressions and had an inverse clinicopathological features. The newly identified miR-146a/WASF2 axis may provide a novel therapeutic target for GC.

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