Purpose: As a novel genetic biomarker, little information is available about the possible role of SPINDOC in different malignant tumors and in hepatocellular carcinoma (HCC).
Methods: Based on The Cancer Genome Atlas (TCGA) database, the expression level of SPINDOC in pan-cancer and hepatocellular carcinoma samples was first determined using bioinformatics analysis. The potential relationship between the expression level as well as the clinical characteristics and the molecular mechanisms through which SPINDOC can promote the proliferation, invasion and migration of HCC cells was evaluated. In addition, cell-based studies and in vivo experiments were used to verify the bioinformatics analysis results.
Results: Bioinformatics analysis showed that SPINDOC expression was significantly increased in 18 human malignancies and the gene expression level was positively correlated with poor clinical prognosis in kidney renal papillary cell carcinoma (KIRP), pheochromocytoma and paraganglioma (PCPG) and liver hepatocellular carcinoma (LIHC). The main type of genetic variation of SPINDOC was amplification, and the increase of SPINDOC mRNA expression level was directly related to the amplification of this gene. The expression level of SPINDOC in patients with primary HCC was positively correlated with poor clinical prognosis, as well as the clinical grade and stage of carcinoma. Gene set enrichment analysis (GSEA) analysis showed that high expression of SPINDOC could activate Wnt/β-catenin signaling pathway. Moreover, in vitro and in vivo experiments showed that SPINDOC gene silencing significantly inhibited the proliferation, migration and invasion of Huh7 and SK-HEP-1 cells and decreased the expression of SPIN1, Wnt1, β-catenin and cyclin D1 but increased the expression of AXIN2.
Conclusion: SPINDOC is highly expressed in pan-cancer and HCC samples. This factor can effectively promote the invasion and migration of hepatocellular carcinoma (HCC) cells by activating Wnt/β-catenin signaling pathway, and thus can serve as a potential therapeutic target for HCC management.
Keywords: SPINDOC , SPIN1, Wnt/ß-catenin, pan-cancer, hepatocellular carcinoma