Background
Kinetochore localized astrin/SPAG5 binding protein (KNSTRN) plays an important molecular in cell division. Mutations of KNSTRN can interfere with chromatid cohesion, increase aneuploidy in tumors, enhancing tumorigenesis. Additionally, the concept of nuclear activating miRNA (NamiRNA) has been proposed with encouraging results. However, the role of KNSTRN in Hepatocellular Carcinoma (HCC) remains not fully determined, and the underlying molecular mechanisms of this differential regulation of KNSTRN by a NamiRNA are also unclear in HCC.
Methods
Based on Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, we first investigated the potential oncogenic functions of KNSTRN and a potential NamiRNA Using R and various computational tools in HCC.
Results
Detailed results revealed that elevated expression of KNSTRN was considerably associated with bad overall survival (HR = 1.48, 95%CI 1.05–2.09, P = 0.027) and progress free interval (HR = 1.41, 95%CI 1.05–1.89, P = 0.021) in HCC. GO/KEGG functional enrichment analysis showed that KNSTRN is closely related to organelle fission, chromosomal region, tubulin binding, and cell cycle signaling pathway. TIMER databases analysis showed the correlations between KNSTRN expression and tumor-infiltrating immune cells, biomarkers of immune cells and immune checkpoint expression. Moreover, KNSTRN level was significantly positively associated with immunosuppressive cell in tumor microenvironment (TME), including regulatory T cells (Tregs), myeloid derived suppressor cells (MDSCs), and cancer-associated fibrocytes (CAFs). Further, hsa-miR-107 is determined as a potential Nuclear activating miRNA (NamiRNA) by correlation analysis. High expression of hsa-miR-107 is negatively correlated with disease specific survival (HR = 0.62, 95%CI 0.4–0.98, P = 0.04) in patients with HCC by targeting the oncogene, KNSTRN. Finally, a possible NamiRNA-enhancer network of hsa-miR-107 activates the KNSTRN expression in LIHC were constructed.
Conclusion
The hsa-miR-107-mediated upregulation of KNSTRN correlated with poor prognosis and tumor immune infiltration in HCC.