MSI2 exerts antitumor effects by regulating T-cell function in kidney renal clear cell carcinoma

Musashi 2 (MSI2) exhibits oncogenic effects in various solid tumors. However, its mechanism of action in kidney renal clear cell carcinoma (KIRC) remains unclear. Our study objective is to explore the expression of MSI2 in KIRC and its relationship with the tumor microenvironment (TME).

We analyzed MSI2 expression at the messenger ribonucleic acid (mRNA) and protein levels using the TIMER2.0 and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) databases, respectively. We also validated the expression and role of MSI2 in renal cells in cell-based experiments and examined the relationship between MSI2 expression and prognosis and the immune microenvironment. Furthermore, we performed an enrichment analysis and constructed regulatory networks for MSI2 to explore its functions and regulatory mechanisms. Finally, we conducted single-cell RNA sequencing (scRNA-seq) to identify key cells in KIRC and a pseudotemporal analysis to investigate their differentiation trajectories.

While MSI2 and its mRNA are typically upregulated in other cancers, they are downregulated in KIRC. A Kaplan-Meier (KM) analysis showed that KIRC patients with high MSI2 expression exhibited improved survival rates. MSI2 was mainly expressed in renal tubules in normal renal tissue and not in KIRC cells. Knocking down MSI2 promoted KIRC cell proliferation, invasion, and migration in vitro, and there was a correlation between MSI2 expression and immune cells and checkpoints. The scRNA-seq analysis indicated that T cells are key players in KIRC. A dynamic MSI2 expression pattern was observed during T-cell differentiation, showing an upward trend in the medium term before leveling off.

Our results suggest that MSI2 plays an antitumor role in KIRC by regulating T-cell function. They also indicate that MSI2 is involved in hydrogen ion secretion in renal tubular epithelial cells and that it may be a differentiation and maturation marker in these cells.