The Expression of NXPH4 in Hepatocellular Carcinoma Tissues and Its Impact on the Biological Functions of Hepatic Cancer Cells

Abstract

Background: There is an urgent need for reliable biomarkers for early detection and effective therapeutic targeting of hepatocellular carcinoma (HCC). This investigation aimed to elucidate neurexophilin 4 (NXPH4) expression in HCC and explore its impact on the biological functions of HCC cells. Methods: This research employed publicly available transcriptomic data from The Cancer Genome Atlas (TCGA) database to evaluate the expression profiles of the NXPH family members in HCC. We collected 70 HCC tissue samples and assessed NXPH4 expression levels using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis, and immunohistochemistry. Furthermore, HCC cell lines with overexpressed and knocked down NXPH4 were established. Methyl thiazolyl tetrazolium (MTT) assay and colony formation analysis were conducted to assess the proliferation and colony formation capabilities of the HCC cells. Additionally, scratch assays and transwell experiments were employed to elucidate the migration and invasion capabilities of these cells. Results: NXPH4 showed significant differential expression in HCC compared to adjacent non-cancerous tissues (p < 0.001), which was associated with overall patient survival (p < 0.001). Moreover, the knockdown of NXPH4 (shNXPH4-1 and shNXPH4-2) significantly suppressed the proliferation and clonogenicity of HepG2 HCC cells (p < 0.01). Conversely, transfection with an overexpression vector (Ov-NXPH4) substantially elevated the proliferation and clonogenicity of Hub-7 cells (p < 0.01). Furthermore, knockdown of NXPH4 (shNXPH4-1 and shNXPH4-2) significantly suppressed the migration and invasion of HepG2 cells (p < 0.01), while its overexpression vector (Ov-NXPH4) significantly promoted these capabilities (p < 0.01). Conclusion: Elevated expression of NXPH4 in HCC regulates crucial biological processes, such as proliferation, migration, and invasion, suggesting its potential role as a biomarker for the progression of hepatocellular carcinoma.