TRNA-Derived Small RNA Accelerates Tumorigenesis through Crosstalk with Tumor-Associated Macrophages, and Downregulation with Cell Membrane-Modified Polymer Nanoparticles Enables Treatment Response.

ABSTRACT: Accumulating evidence has shown that tRNA-derived small RNAs (tsRNAs) play pivotal roles in the progression of the majority of malignancies. The tumor microenvironment (TME) is important for hepatocellular carcinoma (HCC) progression. However, how tsRNAs exert their effects through the TME to drive hepatocarcinogenesis is unclear. We revealed that tsr_019759, a tsRNA, was significantly upregulated in HCC, and it promoted HCC growth and metastasis via inhibiting TNFSF15 expression and activating the JAK2/STAT3 signal pathway. Moreover, tsr_019759 could impede the exocrine secretion of TNFSF15, thereby inducing tumor-associated macrophage (TAM) polarization toward the M2 type through inhibiting the DR3/NF-κB signaling pathway. Additionally, M2 TAMs further facilitated HCC development through

SUBMITTER: Zhou Z 

PROVIDER: S-EPMC12291082 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature