Human WNT5A adenoviral particles

microRNA (miR)-374a plays a crucial role in cancer progression by promoting metastasis and proliferation of multiple malignancies. Here, researchers investigated whether miR-374a affects the progression of bladder cancer and investigated the underlying mechanisms. Low levels of miR-374a were associated with poor prognosis in bladder cancer patients with distant metastasis by in silico analysis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. In T24 and TCCSUP human bladder cancer cells, miR-374a mimics abolished the metastatic potential and invasiveness of bladder cancer cells by downregulating WNT5A; whereas the opposite was observed with miR-374a inhibitors. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of β-catenin. Cisplatin treatment significantly increased the rate of apoptosis. The expression levels of cancer stem cell-related proteins were reduced in cells pretreated with miR-374a mimics. Therefore, these studies indicate that miR-374a can improve the tumor biological behavior of bladder cancer cells, suggesting that miR-374a may be a new small molecule therapeutic target.

Here, after the researchers introduced an adenoviral vector overexpressing WNT5A (Ad-WNT5A) into T24 cells, WNT5A transcripts were significantly upregulated (Figure 1A). Functionally, overexpression of WNT5A exacerbated the metastasis and invasiveness of T24 cells in wound healing and Transwell assays (Figure 1B-D). In addition, treatment with miR-374a mimics significantly abolished the metastatic capacity and invasiveness of T24 cells (Figure 1B-D). Therefore, both miR-374 and WNT5A can alter bladder cell biology. To determine whether the effects of miR-374a on cancer cell biology are achieved through WNT5A downregulation, T24 cells overexpressing WNT5A were treated with miR-374a mimics. First, miR-374a mimics significantly abolished the increase in WNT5A (Figure 1B-D). Second, the increased metastasis and invasiveness of T24 cells induced by WNT5A overexpression were also inhibited (Figure 1B-D). Similar results were observed in TCCSUP cells.

Figure 1. miR-374a mimic decreases metastatic and invasive abilities in bladder cancer cells via degeneration of WNT5A. (Chen X, et al., 2018)