bims-migras 2025-09-07 papers

Issue of 2025–09–07
two papers selected by
Cliff Dominy

Front Immunol. 2025 ;16 1638792

Integrative bulk and single-cell transcriptomic analysis identifies a migrasome-associated lncRNA signature predictive of prognosis and immune landscape in clear cell renal cell carcinoma.

Junlin Shen, Chun Wang, Mingpeng Zhang, Bin Chen, Liwei Liu, Jing Tian, Zhiqun Shang.

Introduction: Clear cell renal cell carcinoma (ccRCC) is characterized by high recurrence and metastasis rates, leading to poor prognosis. Migrasomes, a class of organelles mediating intercellular communication, and long noncoding RNAs (lncRNAs) both play critical roles in tumor progression; however, the prognostic significance of migrasome-associated lncRNAs in ccRCC remains unclear.
Methods: Migrasome-associated lncRNAs were identified using The Cancer Genome Atlas (TCGA) dataset, and a prognostic risk signature was constructed. The associations between the model and overall survival (OS), functional enrichment, tumor mutation burden (TMB), tumor microenvironment (TME) characteristics, immune evasion, and drug sensitivity were evaluated. Single-cell transcriptomic analysis was performed to determine cell type-specific expression patterns and intercellular communication networks. Functional roles of key lncRNAs were validated in vitro using qRT-PCR, CCK-8 proliferation assays, wound-healing assays, Transwell assays, colony formation assays, immunofluorescence, and Western blotting.
Results: The risk signature stratified patients into high- and low-risk groups with significantly different survival outcomes. High-risk patients exhibited elevated TMB and enhanced immune evasion potential. Drug sensitivity analysis revealed distinct therapeutic response profiles between the groups. Single-cell transcriptomic analysis uncovered pronounced cellular heterogeneity and TME characteristics associated with the prognostic signature. High-risk cells were predominantly enriched within tumor epithelial clusters and displayed distinct intercellular communication patterns. Knockdown of FOXD2-AS1 markedly suppressed tumor cell proliferation and migration and reduced the expression of migrasome marker proteins.
Discussion: This study presents a novel migrasome-associated lncRNA risk signature with significant prognostic and therapeutic implications for ccRCC. The signature captures distinct immune, genomic, and pharmacologic features, and its core lncRNAs may promote tumor progression through migrasome-mediated signaling pathways, warranting further mechanistic investigation.

Keywords: clear cell renal cell carcinoma; drug sensitivity; migrasome; prognostic signature; single-cell RNA sequencing; tumor immune microenvironment; tumor mutation burden

DOI: https://doi.org/10.3389/fimmu.2025.1638792

Exp Cell Res. 2025 Sep 02. pii: S0014-4827(25)00329-5. [Epub ahead of print] 114729

tsRNA-10105-enriched Migrasomes Mediate Hepatocellular Carcinoma Immunosuppressive Microenvironment by Inducing M2 Macrophage Polarization.

Ruiyao Zhou, Limin Pan, Yu Zeng, Yu Zhou, Haifeng Zhang, Shengguo Zhang, Xiao Hu.

Hepatocellular carcinoma (HCC) is characterized by a complex immunosuppressive microenvironment, which significantly influence tumor progression. Migrasomes, newly identified extracellular vesicles, have emerged as a novel mode of intercellular communication. However, their roles in HCC immune microenvironment are rarely studied. Here, we observed the migrasome markers and M2 polarization levels in HCC patient tissues using immunofluorescence. Migrasomes were isolated from HCC cells and characterized using electron microscopy, immunofluorescence, and Western blot. The effects of migrasomes on macrophage polarization and HCC progression were investigated in vitro and in vivo. Small RNA-seq was conducted to screen for key tsRNA. We discovered that the levels of the migrasome marker and M2 macrophage marker were elevated in liver tumor tissues. Migrasomes derived from HepG2 induced macrophage M2 polarization, as indicated by the increased expression of M2 polarization marker, and the suppressed expression of M1 polarization marker. Macrophages treated with these migrasomes further stimulated the proliferation, migration, and invasion of malignant cells in vitro and augmented tumor growth and metastasis in vivo. Compared to the healthy individuals, the sera of HCC patients demonstrated elevated expression of tsRNA-10105 in migrasomes. Inhibition of tsRNA-10105 significantly abolished the inducing effect of cancer cell migrasomes on the M2 macrophages polarization. Our findings indicate that migrasome-derived tsRNA-10105 from HCC cells can induce the M2 macrophages polarization, which in turn augments survival and migration of HCC cells. This work provides insights into the mechanisms of the immunosuppressive microenvironment in HCC and offers novel perspectives for the immunotherapy of liver cancer.

Keywords: Hepatocellular carcinoma; Immunosuppressive microenvironment; M2 macrophage polarization; Migrasome; tsRNA

DOI: https://doi.org/10.1016/j.yexcr.2025.114729