KHSRP promotes cancer stem cell maintenance, tumorigenesis, and suppresses anti-tumor immunity in gastric cancer.

Abstract

Objectives: KH-type splicing regulatory protein (KHSRP) is an RNA-binding protein involved in several cellular processes, including nuclear splicing, mRNA localization, and cytoplasmic degradation. While KHSRP's role has been studied in other cancers, its specific involvement in gastric cancer remains poorly understood. This study aims to explore KHSRP expression in gastric cancer and its potential effects on tumor progression and immune response.

Methods: KHSRP expression in gastric cancer tissues and normal tissues was analyzed using data from The Cancer Genome Atlas (TCGA) database. The correlation between KHSRP expression, patient survival, and immune response was also assessed. Immunohistochemistry was performed to evaluate KHSRP expression in gastric cancer tissues. Gain- and loss-of-function experiments were conducted to assess KHSRP's effects on gastric cancer cell proliferation, stemness, and migration. Furthermore, the impact of KHSRP silencing on tumor volume and immune cell infiltration was evaluated in a C3H/He mouse xenograft model.

Results: KHSRP was found to be overexpressed in gastric cancer tissues compared to normal tissues, with a positive correlation to tumor stage and a negative correlation with patient prognosis. Functional assays revealed that KHSRP promotes gastric cancer cell proliferation, enhances cancer stem cell properties, and increases migratory capabilities in vitro. In vivo, KHSRP silencing led to a significant reduction in tumor volume and increased immune cell infiltration in the mouse xenograft model.

Conclusions: KHSRP acts as an oncogene in gastric cancer by promoting tumorigenesis and suppressing anti-tumor immune responses. Its overexpression is associated with poor prognosis, making KHSRP a potential prognostic marker and therapeutic target in gastric cancer.