bims-exocan 2026-05-03 papers

Issue of 2026–05–03
five papers selected by
Muhammad Rizwan, COMSATS University

Biochem Biophys Res Commun. 2026 Apr 21. pii: S0006-291X(26)00593-0. [Epub ahead of print]819 153829

Exosome-derived hsa-miR-21-5p stimulates malignant progression of colorectal cancer by regulating HRK.

Shengyong You, Lingyun Gu, Huirong Wu, Cuihua Wu.

Exosome-mediated microRNAs (miRNA) delivery is increasingly recognized as a central mechanism in tumor microenvironment (TME) remodeling. While the pro-tumorigenic role of tumor cell-derived exosomal miRNAs in colorectal cancer (CRC) is established, their specific regulatory mechanisms require further elucidation. In this study, we demonstrate that exosomes originating from CRC cells not only markedly enhance the proliferation, migration, and invasion capacities of recipient CRC cells but also lead to the suppression of apoptosis in the recipient cells. By means of integrated public database analysis and RT-qPCR validation in clinical tissue samples, researchers confirmed that miR-21-5p is a key oncogenic regulator. Subsequent RT-qPCR analysis of clinical serum exosomes and CRC cells incubated with CRC-derived exosomes revealed significant enrichment of miR-21-5p within these exosomes. HARAKIRI (HRK) was found to serve as a putative downstream target for miR-21-5p. Bioinformatics analysis and examination of clinical CRC tissues demonstrated significant downregulation of HRK in tumors, which correlated negatively with miR-21-5p expression. The direct targeting and repression of HRK expression by miR-21-5p were ascertained through luciferase reporter assays and functional validation experiments. Mechanistically, CRC-derived exosomes deliver miR-21-5p into CRC cells, leading to HRK suppression. This downregulation relieves inhibition of Bcl-2, thereby promoting the malignant progression of CRC cells. Notably, in vivo HRK overexpression partially rescued the tumor growth-promoting effect of CRC-derived exosomes. Collectively, our findings elucidate a novel exosomal miR-21-5p/HRK/Bcl-2 signaling axis in CRC progression, while supplying putative diagnostic and therapeutic targets for this malignancy.

Keywords: Bcl2; Colorectal cancer; Exosomes; HRK; miR-21-5p

DOI: https://doi.org/10.1016/j.bbrc.2026.153829

Discov Oncol. 2026 Apr 29.

Functions and mechanisms of exosomal lncRNAs in esophageal cancer.

Sajad Ehtiati, Behnam Ravanbakhsh, Hassan Ghasemi, Mahsa Salehi, Farideh Ghalamfarsa, Sara Zafaranchi Zm, Farzaneh Vahedi, Mortaza Taheri-Anganeh, Ahmad Movahedpour, Gholamabbas Sabz, Saleh Aiiashi.

Esophageal cancer is a prevalent and highly aggressive malignancy with poor clinical outcomes, largely due to late diagnosis and limited effective biomarkers. Improved understanding of its molecular mechanisms and the identification of reliable non-invasive diagnostic indicators are therefore of critical importance. Exosomes are small double-membrane extracellular vesicles present in various biological fluids that mediate intercellular communication through the transfer of bioactive cargo, including proteins and RNAs. Among these cargos, long non-coding RNAs (lncRNAs) packaged within exosomes have emerged as key regulators of tumor initiation, progression, metastasis, and therapeutic resistance. Increasing evidence indicates that exosomal lncRNAs play crucial roles in esophageal cancer by modulating cell proliferation, migration, invasiveness, angiogenesis, and response to treatment, while also exhibiting high stability in circulation, making them promising diagnostic and prognostic biomarkers. This review summarizes recent advances in the biological functions, clinical relevance, and translational potential of exosomal lncRNAs in esophageal cancer, highlighting their emerging value in liquid biopsy and targeted therapeutic strategies.

Keywords: Cancer; Esophageal cancer; Exosomes; IncRNA; miRNA

DOI: https://doi.org/10.1007/s12672-026-05079-w

Semin Oncol. 2026 Apr 03. pii: S0093-7754(26)00044-8. [Epub ahead of print]53(4): 152497

Exosomes as emerging biomarkers in breast, lung, and colorectal cancer diagnosis: A comprehensive review.

Irem Yildirim, Cigir Biray Avci.

Although exosome research has advanced considerably, clinical implementation remains limited. In contrast to previous reviews that catalog numerous biomarkers, this review focuses on translationally ready candidates for breast, lung, and colorectal cancers. Exosomal signatures address key diagnostic challenges, such as enabling tissue-free molecular subtyping in breast cancer, distinguishing malignant from benign nodules in lung cancer, and detecting CEA-negative or premalignant adenomas in colorectal cancer. This review critically assesses clinically advanced biomarkers-including miRNAs, lncRNAs, circRNAs, and proteins-and highlights those with validated, high diagnostic performance relative to current standards (e.g., CEA, imaging). Single biomarkers often fail to capture tumor heterogeneity, whereas multi-omic panels integrated with clinical data improve diagnostic accuracy. Exosomal biomarkers should, therefore, be considered adjuncts to standard diagnostics, functioning as triage tools to enhance patient management. The integration of exosomes into clinical workflows holds significant promise for non-invasive, early cancer detection, and personalized medicine.

Keywords: Breast cancer; Cancer diagnosis; Colorectal cancer; Exosomes; Lung cancer

DOI: https://doi.org/10.1016/j.seminoncol.2026.152497

Cells. 2026 Apr 20. pii: 731. [Epub ahead of print]15(8):

Exosomal microRNAs in Bronchial Aspirate and Other Liquid Biopsy Specimens for Lung Cancer: Current Evidence and Future Perspectives-A Narrative Review.

Dragoș Huțanu, Mara Andreea Vultur, Corina Eugenia Budin, Dumitru Cătălin Sârbu, Maria Beatrice Ianoși, Edith Simona Ianoși, Hédi Katalin Sárközi, Gabriela Jimborean.

Lung cancer remains the leading cause of cancer mortality worldwide, with most cases diagnosed at advanced stages. Conventional tissue biopsy is invasive, and low-dose CT (LDCT) screening-although effective-faces practical and logistical limitations. Liquid biopsy has emerged as a minimally invasive approach to capture tumor-derived material, including circulating tumor DNA (ctDNA), cells, and extracellular vesicles (EVs). Among EVs, exosomes and their microRNA (miRNA) cargo offer a stable, disease-specific signal. Airway-proximal fluids such as bronchial aspirate and bronchoalveolar lavage fluid (BALF) are in direct contact with the tumor microenvironment and may contain higher concentrations of tumor-derived exosomal miRNAs compared with blood. This review synthesizes the limited but promising evidence for exosomal miRNAs in bronchial aspirate and BALF as diagnostic and prognostic biomarkers in lung cancer, examines methodological and standardization challenges, and discusses potential integration into clinical workflows, with particular emphasis on Romania's lung cancer epidemiology and healthcare context. While only two primary studies in the last five years have explored BALF exosomal miRNAs, these data justify further multicenter investigations aligned with MISEV2023 guidelines. Integrating airway-proximal exosomal miRNA analysis into bronchoscopy procedures could enhance diagnostic precision in resource-limited health systems and support the transition towards personalized thoracic oncology.

Keywords: cancer; exosomes; lung cancer; micro-ARN

DOI: https://doi.org/10.3390/cells15080731

Front Biosci (Landmark Ed). 2026 Apr 21. 31(4): 46312

CD44+ and CD133+ Extracellular Vesicles as Future Potential Targets in Gastrointestinal Tumor.

Cristina Pizzulli, Beatrice Menicacci, Margherita Parrini, Edoardo Tonelli, Caterina Bartolini, Armando Curto, Giulia Petroni, Serena Pillozzi, Andrea Galli.

Extracellular vesicles (EVs) are small nanometric particles surrounded by a lipid bilayer and actively secreted by different cell types. EVs play a key role in cell-to-cell communication, and the vast array of biomolecules that EVs transport reflects the molecular profile of the originating cells. In cancer, EVs are key components of the tumor microenvironment (TME); meanwhile once released into the peripheral circulation, EVs can travel systemically and transmit signals beyond the primary tumor site, making EVs ideal candidates for liquid biopsy. Notably, EVs can be isolated from a blood sample and analyzed to obtain real-time information on tumor biology, enabling early diagnosis, monitoring of treatment response, and evaluation of disease evolution, with high sensitivity and specificity. This review examines the biological significance and clinical utility of EVs expressing the stemness-associated glycoproteins CD44 and CD133 in gastrointestinal (GI) malignancies. Cancer stem cells (CSCs) expressing these surface markers are known to exhibit enhanced tumorigenic potential, metastatic capacity, and therapy resistance. In particular, we focus on the increasing evidence that EVs enriched in CD44+ and CD133+ populations play critical roles in key aspects of tumor progression in cholangiocarcinoma, pancreatic, colorectal, and gastric cancers. Following internalization by recipient cells, CD44+ and CD133+ EVs drive phenotypic reprogramming, foster more aggressive cellular states, and promote chemoresistance by delivering specific molecular cargo. Mechanistically, CD44 isoforms, particularly CD44v6 and CD44v9, activate key oncogenic signaling pathways, including Wnt/β-catenin and phosphoinositide 3-kinase (PI3K)/serine/threonine kinase AKT (AKT). In parallel, CD133-enriched EVs help maintain stemness and contribute to TME reorganization, thereby facilitating tumor progression. Despite ongoing challenges in EV isolation and standardization, EVs positive for stemness markers show great potential as liquid biopsy analytes for noninvasive disease monitoring, prognostic evaluation, and patient stratification. This review summarizes the expanding body of knowledge on cancer stem cell (CSC)-derived EVs in GI tumors, underscoring the potential of these particles for early diagnosis, prognosis, and the development of targeted therapies to overcome treatment resistance.

Keywords: CD133; CD44; biomarkers; cancer stem cells; extracellular vesicles; liquid biopsy

DOI: https://doi.org/10.31083/FBL46312