Abstract：Objective: To explore the effects of WWP2 on the biological behavior of colon cancer cells via regulating of Hippo-Yes-associated protein (YAP) signaling pathway. Methods: Tumor samples and corresponding adjacent normal mucosal tissue samples of 60 patients undergoing radical resection of colon cancer in our hospital from December 2022 to December 2023 were collected, and the expression levels of WWP2 in the samples were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot. The baseline data of age, sex, tumor-node-metastasis (TNM) stage, size, invasion and metastasis of tumor in patients were assessed, the relationship between WWP2 expression level and clinicopathological features of colon cancer were analyzed. The expression of WWP2 in colon cancer and Kaplan-Meier survival curve were evaluated by Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Colon cancer cell line SW620 were grouped according to the protocol, and WWP2 interference expression was grouped as follows: Control group, si-NC group (transfected with si-NC), si-WWP2 group (transfected with si-WWP2) and XMU-MP-1 group (transfected with si-WWP2 and treated with 5 μmol/L XMU-MP-1 in the medium). WWP2 ove-rexpression was grouped as follows: Control group, LV-NC group (transfected with LV-NC), LV-WWP2 group (transfected with LV-WWP2) and MY-875 group (transfected with LV-WWP2 and treated with 20 nmol/L MY-875 in the medium). The cell proliferation activity, cell clones number, cell invasion, and migration were detected by MTT assay, plate cloning assay, Transwell assay, and scratch healing assay, respectively. The proteins expression levels of WWP2 and Hippo-YAP signaling pathways were detected by Western blot. Results: Compared with paracancer tissue, the mRNA and protein expression levels of WWP2 were significantly increased in colon cancer tissues (P<0.05), and WWP2 was a negative correlation factor for survival and prognosis of patients with colon cancer (HR>1), and its expression level was closely correlated with tumor size (P=0.023), differentiation degree (P=0.01), invasion degree (P=0.011) and lymph node metastasis (P=0.006). Compared with the si-NC group, the mRNA and protein expression levels of WWP2 in si-WWP2 group were significantly decreased (P<0.05), the clone number, cell mobility and invasion were significantly decreased (P<0.05), and protein phosphorylation levels of MST1, LATS1 and YAP were significantly increased (P<0.05). Compared with si-WWP2 group, the mRNA and protein expression levels of WWP2 in XMU-MP-1 group were significantly increased (P<0.05), the clone number, cell mobility and invasion were significantly decreased were significantly increased (P<0.05), and protein phosphorylation levels of MST1, LATS1 and YAP were significantly decreased (P<0.05). Compared with LV-NC group, the mRNA and protein expression levels of WWP2 in LV-MMP2 group were significantly increased (P<0.05), the clone number, cell mobility and invasion were significantly decreased were significantly increased (P<0.05), and protein phosphorylation levels of MST1, LATS1 and YAP were significantly decreased (P<0.05). Compared with the LV-WWP2 group, the mRNA and protein expression levels of WWP2 in MY-875 group were significantly decreased (P<0.05), the clone number, cell mobility and invasion were significantly decreased were significantly decreased (P<0.05), and protein phosphorylation levels of MST1, LATS1 and YAP were significantly increased (P<0.05). Conclusion: WWP2 may be a promoter of colon cancer and is closely associated with poor prognosis. Down-regulating WWP2 expression can affect the malignant progression of colon cancer by inhibiting the proliferation, migration and invasion of colon cancer cells, which may be related to the activation of Hippo-YAP signaling pathway.
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2025, Vol. 31 
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