GSE158262
RNA-sequencing reveals signaling pathways associated with tumor invasion and epithelial–mesenchymal transition in HIPK2-attenuated cells
Homeodomain-interacting protein kinase 2 (HIPK2), a well-known tumor suppressor, exhibits contradictory expression patterns in different cancers. This study was performed to reveal the potential mechanism of HIPK2 involvement in oral squamous cell carcinoma (OSCC) metastasis.  High throughput RNA-sequencing was used to detect the dysregulated signaling pathways in HIPK2 deficiency OSCC cells. Transwell assay and lymphatic metastatic orthotopic mouse model assay were performed to identify the effect of HIPK2 on tumor invasion. Western blotting and luciferase reporter assay were performed to examine the HIPK2/P53/E-Cadherin axis in OSCC. We observed that depletion of HIPK2 promoted tumor cell invasion in vitro and facilitated cervical lymph node metastasis in vivo. According to mRNA-sequencing, pathways closely related to tumor invasion were notably activated. HIPK2 was found to trigger E-Cadherin expression by mediating P53, which directly targets the CDH1 (coding E-Cadherin) promoter. Restoring P53 expression rescued the E-Cadherin suppression induced by HIPK2 deficiency. Together, the depletion of HIPK2 expression promoted OSCC metastasis by suppressing the P53/E-Cadherin axis, which might be a promising target for anti-cancer therapies. Overall design: RNA-seq in the Cal-27 cell line before and after knockdown of HIPK2