Revealing splenectomy-driven microRNA hsa-7b-5p’s role in pancreatic cancer progression

• DOI: 10.1016/j.isci.2024.109045
• Publication Date: 2024-01-26T21:07:53Z
• Authors: Liangliang Wu; Yongjie Xie; Bo Ni; Peng Jin; Bin Li; Mingzhi Cai; Baogui Wang; Chengyan Wu; Yuexiang Liang; Xiaona Wang
• Keywords: 0301 basic medicine; 0303 health sciences; Science; Immunology; Q; Transcriptomics; Article; Cancer

Splenectomy often accompanies distal pancreatectomy for pancreatic cancer. However, debates persist on splenic function loss impact. Prior studies in mice revealed splenectomy promotes pancreatic cancer growth by altering CD4/Foxp3 and CD8/Foxp3 ratios. The effect on other immune cells remains unclear. Clinical observations indicate splenectomy induces immunosuppression, heightening recurrence and metastasis risk. Here, we established an orthotopic pancreatic cancer model with splenectomy and observed a significant increase in tumor burden. Flow cytometry revealed elevated MDSCs, CD8+PD-1high+ T cells, and reduced CD4+ T cells, CD8+ T cells, and natural killer cells in tumors. Bulk sequencing identified increased MicroRNA (miRNA) hsa-7b-5p post-splenectomy, correlating with staging and immunosuppression. Similar results were obtained in vivo by constructing a KPC-miRNA hsa-7b-5p-sh cell line. These findings suggest that splenectomy enhances the expression of miRNA hsa-7b-5p, inhibits the tumor immune microenvironment, and promotes pancreatic cancer growth.