ORC6 Exerts Oncogenic Functions in Kidney Renal Clear Cell Carcinoma by Regulating Cell Proliferation and Apoptosis: A Prognostic and Immunological Indicator for Future Clinical Interventions.

With the application of precise clinical interventions in tumor treatment, it is of great value to explore novel biomarkers and their underlying molecular mechanisms. In this paper, we firstly explored the prognostic, immunological features, functions, and potential mechanisms of ORC6 in kidney renal clear cell carcinoma (KIRC) via single-cell and bulk RNA sequencing. Single-cell and bulk RNA sequencing data related to ORC6 data in KIRC were acquired from shared online databases. Spearman correlation analyses were carried out to investigate the relationships between ORC6 expression and interested targets, including tumor mutation burden (TMB), tumor microenvironment, and immunotherapy responses. Besides, the expression pattern of ORC6 and its role in KIRC were verified in vitro experiments. Also, the potential mechanisms and regulatory upstream of ORC6 in KIRC were explored. ORC6 was up-regulated in KIRC samples compared with normal tissues, validated by PCR analyses of KIRC tissues and cell lines (p < 0.05). Single-cell RNA sequencing analysis showed that ORC6 was mainly expressed in immune T cells. Survival and Cox regression analysis showed ORC6 had prognostic values in KIRC (p < 0.05). Correlation analysis revealed ORC6 was strongly correlated with immunity and immunotherapy sensitivity (p < 0.05). Further experiments in vitro indicated that ORC6 could regulate the cell proliferation/apoptosis of KIRC. Finally, a putative long non-coding RNA (LncRNA)/RNA binding protein (RBP)/ORC6 regulatory network was identified to explore ORC6-related potential upstream regulatory mechanisms in KIRC. In conclusion, ORC6 might play oncogenic roles in KIRC and regulate cell proliferation/apoptosis in KIRC. Furthermore, ORC6 showed significant associations with immunity and potential immunotherapy sensitivity. These findings provided a foundation for future studies evaluating the clinical significance of ORC6 in KIRC.