Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.06.13.659272

Identification of novel exosomal miRNAs and their role in diagnosis and prognosis of Triple Negative Breast Cancer

Abstract

Triple-negative breast cancer (TNBC) is a clinically aggressive subtype with poor prognosis and limited treatment options. Exosomal microRNAs (miRNAs), encapsulated within secretory vesicles, have emerged as promising biomarkers for cancer detection and monitoring. In this study, we identify five novel exosomal miRNAs--hsa-miR-6803, hsa-miR-1180, hsa-miR-4728, hsa-miR-1915, and hsa-miR-940--that are consistently overexpressed in TNBC cells, stem-like subpopulations, and patient tumor tissues. Integrated analysis of public datasets and in vitro validation revealed that elevated expression of these miRNAs correlates with poor overall survival. Functional assays demonstrated that miR-1180 and miR-4728 significantly promote TNBC cell migration and invasion. These miRNAs also target critical oncogenic pathways, including Wnt, Notch, and EGFR. Their enrichment in exosomes highlights their translational potential as liquid biopsy-based biomarkers and therapeutic targets. This work is the first to link this miRNA panel to both TNBC tumorigenesis and stem-like cell biology, offering new insights into disease progression and potential strategies for personalized care.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Das, B. C., Choudhary, A., Poojary, S., Jain, P., Chaturvedi, H.. 2025-06-18. Identification of novel exosomal miRNAs and their role in diagnosis and prognosis of Triple Negative Breast Cancer. https://doi.org/10.1101/2025.06.13.659272

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Tissue resident CD4+ memory T-cells mark response to immune checkpoint inhibition in high-grade glioma

Background: Immune checkpoint inhibitors (ICI) are efficacious in many solid tumors, but response in glioma is restricted to a small subgroup. The determinants of response and resistance to ICI remain poorly understood. Methods: Here we exploit a syngeneic hypermutated high-grade glioma model with dichotomous response to combined PD-1 and CTLA-4 inhibition to unravel determinants of tumor-infiltrating T-cells driving response. Tumor-infiltrating T-cells from ICI-responsive and non-responsive tumors were analyzed by single-cell RNA and T-cell receptor sequencing and tumor-reactive T-cell receptor clonotypes were functionally validated to characterize their transcriptional phenotypes. We verify our findings in IDH1 wildtype glioblastoma patients treated with neoadjuvant pembrolizumab. Results: ICI response was associated with intratumoral clonal expansion of tumor-reactive cytotoxic T-cells and increased infiltration of CXCR6+ CD4+ tissue resident memory T-cells (Trm). CD4 stem-like memory T-cells in responding tumors demonstrated elevated interferon responses, following trajectories toward clonally expanded Trm, versus trajectories toward exhaustion in non-responsive tumors. In responsive tumors, CD4+ Trm interacted with infiltrating CXCR3+ tumor-reactive and clonally expanded, yet transcriptionally versatile cytotoxic T-cells. Probing the post neoadjuvant ICI high-grade glioma patient tissue dataset, we confirmed increased CXCR6 expression in CD4+ T cells and the association of CD4+ Trm with prolonged overall survival. Conclusion: These findings identify CD4 tissue-resident memory T-cells as determinants of ICI response in IDH1 wildtype high-grade glioma and warrant their further investigation to improve immunotherapy outcomes.

cancer biology↗

Circadian gene-network distortion in high-risk neuroblastoma across multiple biological reference contexts

Background: The circadian clock regulates cellular homeostasis, and its disruption has been implicated in aggressive neuroblastoma, particularly in tumours harbouring MYCN- amplification. However, it remains unclear whether alterations are restricted to individual clock genes or extend to circadian gene network coordination. We therefore examined circadian clock network disruption in adverse neuroblastoma across multiple biological contexts. Methods: We estimated circadian gene network dysregulation using Delta-CCD in tumours from two neuroblastoma cohorts (SEQC n=498 and Kocak n=649), comparing clinical features associated with outcome across canonical, adrenal-tissue matched, and developmental references. Robustness was assessed by cross-cohort meta-analysis and leave-one-gene-out analyses. Cox proportional hazards models adjusted for clinical covariates assessed association between individual clock gene expression patient outcome. Results: Delta-CCD was highest in tumours classified as high-risk (study-specific definition) across reference contexts in both cohorts. MYCN-amplified tumours showed a more reference-dependent pattern, strongest in adrenal context, while stage 4 tumours showed a similar but weaker pattern. Additional analyses supported the high-risk signal as a distributed network-level alteration rather than a single-gene phenomenon. Conclusions: High-risk neuroblastoma is characterised by robust disruption of coordinated clock gene network organisation across canonical and tissue-matched references, extending beyond individual clock genes. The extent of circadian dysregulation depends on the reference state used.

cancer biology↗

BAP1 loss and PRAME expression converge to remodel the tumor-immune ecosystem during uveal melanoma progression

Uveal melanoma (UM) is characterized by a small number of recurrent genetic alterations that determine metastatic propensity. BAP1 loss and PRAME expression define the dominant prognostic axes in UM, yet how they promote malignant progression remains unclear. We profiled 190,535 cells from normal uvea, uveal nevus, primary and metastatic UM using single-cell transcriptomics, T cell receptor sequencing, spatial transcriptomics and isogenic perturbation models. Normal melanocytes, nevus cells and UM cells formed a transcriptional continuum marked by loss of differentiation and emergence of neural crest-like, stress-responsive, hypoxic-glycolytic and immune-interacting states. BAP1 loss and PRAME expression imposed distinct but convergent immunoregulatory programs, inducing interferon and TNF-NFkB signaling and MHC-I expression, with HLA-E showing the strongest response. These alterations were accompanied by macrophage and CD8+ T cell remodeling. PRAME-enriched tumor regions formed spatially organized niches enriched for macrophages and plasma cells. These findings define BAP1 loss and PRAME expression as distinct but convergent axes of tumor-immune coevolution and nominate HLA-E as a candidate mediator of immune resistance.

cancer biology↗