The WNT5A gene encodes a secreted glycoprotein belonging to the Wnt family that plays a key role in developmental processes, cell proliferation, and tissue homeostasis. As a non-canonical Wnt ligand, WNT5A primarily activates β-catenin-independent signaling pathways, such as the planar cell polarity (PCP) pathway and the Wnt/Ca²⁺ pathway. It is essential for embryogenesis, limb development, and organogenesis, and its dysregulation is associated with cancer, inflammation, and metabolic disorders. The function of WNT5A is context-dependent, and it can act as both an oncogene and a tumor suppressor depending on the cellular context. Its complex signaling mechanism makes it a key target for regenerative medicine, cancer biology, and stem cell differentiation research.
Human WNT5A adenoviral particles are replication-defective viral vectors designed to efficiently deliver the WNT5A gene into mammalian cells. These viral particles exploit the natural tropism of adenoviruses to transduce a wide range of cell types, including primary cells and cells that are difficult to transfect. To ensure safety, the adenoviral backbone is modified to delete essential viral genes (e.g., E1/E3) to prevent replication while housing the WNT5A transgene under a strong promoter (e.g., CMV or EF1α). Following transduction, cells express the WNT5A protein and can be used to study its signaling cascades, cellular responses, or therapeutic potential. Applications include in vitro functional assays, in vivo gene therapy models, and tissue engineering.
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)
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High Purity & Low Toxicity
The purity of these Human WNT5A adenoviral particles was exceptional, resulting in minimal cellular toxicity in my HEK293 cells. This allowed for cleaner experimental outcomes and reliable data interpretation.
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