Decoding the pancreatic cancer microenvironment: The multifaceted regulation of microRNAs

Clin Transl Med. 2025 Jul;15(7):e70354. doi: 10.1002/ctm2.70354.

Abstract

Pancreatic cancer (PC) is an extremely deadly type of cancer, and the 5-year survival rate remains less than 10%. The tumour microenvironment (TME) affects the occurrence, progression and treatment outcomes of PC. MicroRNAs (miRNAs) are essential to regulate PC TME. This review delves into the different roles of miRNAs in the PC TME, including exosome communication, angiogenesis, interactions with cancer-associated fibroblasts, the immunological and neuronal microenvironments and metabolic reprogramming. However, research on the complex regulatory networks and synergistic effects of miRNAs in the TME is still insufficient, and their clinical translation and application face challenges. This review summarised the activities of miRNAs in the PC TME, guiding future research and therapeutic strategies involving miRNAs in PC. Future studies should integrate advanced technologies to decode the spatiotemporal dynamics of miRNA regulation within the TME and develop optimised nanodelivery systems for stable and targeted miRNA delivery, advancing clinical applications in PC treatment.

Keywords: PC; exosome; immune microenvironment; miRNA; tumour microenvironment.

Publication types

  • Review

MeSH terms

  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / pathology
  • Tumor Microenvironment* / genetics

Substances

  • MicroRNAs