bims-exocan 2024-12-08 papers

Issue of 2024–12–08
three papers selected by
Muhammad Rizwan, COMSATS University

ACS Biomater Sci Eng. 2024 Dec 05.

Circulating Extracellular Vesicles as Promising Biomarkers for Precession Diagnostics: A Perspective on Lung Cancer.

Sunil Vasu, Vinith Johnson, Archana M, K Anki Reddy, Uday Kumar Sukumar.

Extracellular vesicles (EVs) have emerged as promising biomarkers in liquid biopsy, owing to their ubiquitous presence in bodily fluids and their ability to carry disease-related cargo. Recognizing their significance in disease diagnosis and treatment, substantial efforts have been dedicated to developing efficient methods for EV isolation, detection, and analysis. EVs, heterogeneous membrane-encapsulated vesicles secreted by all cells, contain bioactive substances capable of modulating recipient cell biology upon internalization, including proteins, lipids, DNA, and various RNAs. Their prevalence across bodily fluids has positioned them as pivotal mediators in physiological and pathological processes, notably in cancer, where they hold potential as straightforward tumor biomarkers. This review offers a comprehensive examination of advanced nanotechnology-based techniques for detecting lung cancer through EV analysis. It begins by providing a brief overview of exosomes and their role in lung cancer progression. Furthermore, this review explores the evolving landscape of EV isolation and cargo analysis, highlighting the importance of characterizing specific biomolecular signatures within EVs for improved diagnostic accuracy in lung cancer patients. Innovative strategies for enhancing the sensitivity and specificity of EV isolation and detection, including the integration of microfluidic platforms and multiplexed biosensing technologies are summarized. The discussion then extends to key challenges associated with EV-based liquid biopsies, such as the standardization of isolation and detection protocols and the establishment of robust analytical platforms for clinical translation. This review highlights the transformative impact of EV-based liquid biopsy in lung cancer diagnosis, heralding a new era of personalized medicine and improved patient care.

Keywords: Exosomes; biosensors; early detection; liquid biopsy; lung cancer

DOI: https://doi.org/10.1021/acsbiomaterials.4c01323

Ann Hepatol. 2024 Nov 29. pii: S1665-2681(24)00528-3. [Epub ahead of print] 101745

Exosomal linc00152 intensifies the crosstalk between cholangiocarcinoma cells and cancer-associated fibroblasts.

Min Hu, Yaxuan Niu, Jinlin Wang, Xiao Chen, Gang Li.

INTRODUCTION AND OBJECTIVES: Cholangiocarcinoma is a highly lethal carcinoma. Exosomes derived from cancer-associated fibroblasts (CAFs) serve key roles in the crosstalk between CAFs and cancer cells. Exploring the roles of CAF-derived exosomes and the mechanisms contribute to a better understanding of the development of cholangiocarcinoma.
MATERIALS AND METHODS: Carcinoma and para-carcinoma tissues were collected from patients. Exosomes were isolated from CAFs and characterized by transmission electron microscopy, dynamic light scattering and western blot. Cholangiocarcinoma cells were cocultured with CAF-derived exosomes, and its proliferation, migration and invasion were evaluated with CCK-8, EdU incorporation and Transwell assays, respectively. The interaction between a long non-coding RNA linc00152 and an RNA-binding protein hnRNPA2B1 was determined with RNA immunoprecipitation and RNA pull-down. The ubiquitination of hnRNPA2B1 was examined with western blot.
RESULTS: Linc00152 was highly expressed in cholangiocarcinoma tissues and cells, and its increased expression was associated with advanced tumor stage and poor prognosis. Linc00152 was highly enriched in CAFs and CAF-derived exosomes. CAF-derived exosomes promoted cholangiocarcinoma cell proliferation, migration, and invasion by delivering linc00152. Further analysis showed that hnRNPA2B1 recruited linc00152 and enhanced its loading into exosomes. The interaction between hnRNPA2B1 and linc00152 was identified, and linc00152 repressed the proteasome-dependent degradation of hnRNPA2B1 in cholangiocarcinoma cells. The oncogenic activities of linc00152 in cholangiocarcinoma cells were dependent on hnRNPA2B1 upregulation.
CONCLUSIONS: CAF-derived exosomes harboring linc00152 enhance malignancy in cholangiocarcinoma, identifying a novel role of exosomal linc00152 for intensifying the crosstalk between CAFs and cholangiocarcinoma cells.

Keywords: Cancer-associated fibroblasts; Cholangiocarcinoma; Exosomes; hnRNPA2B1; linc00152

DOI: https://doi.org/10.1016/j.aohep.2024.101745

J Biochem Mol Toxicol. 2024 Dec;38(12): e70080

Exosomal miR-20b-5p Induces EMT and Enhances Progression in Non-Small Cell Lung Cancer Via TGFBR2 Downregulation.

Hui Ma, Bo Jiang, Qiu Ren, Yajiao Sun, Mengyao Wang, Siyu Xia, Dong Wang, Wei Zhang.

The mechanism by which specific miRNAs in NSCLC exosomes regulate NSCLC progression remains unclear. First, exosomes were isolated and identified. Exosomes were labeled with PKH26 for cell tracking studies. Subsequently, BEAS-2B cells and BEAS-2B cell exosomes were transfected with miR-20b-5p mimics or miR-20b-5p inhibitors, and cell proliferation was measured by EdU and CCK-8. cell migration and invasion were detected by wound healing tests and Transwell. The potential target of miR-20b-5p was predicted and verified by luciferase assay. Relative expression levels of miR-20b-5p and TGFBR2 were detected by qRT-PCR. Protein expression level was detected by Western blot. In addition, A549 cell exosomes were injected into mice through the tail vein and the pathological changes of lung tissue were detected by HE staining. Expression levels of E-cadherin and Vimentin in lung tissues were detected by immunohistochemistry. Our results also showed that high levels of miR-20b-5p in exosomes generated from NSCLC cells conceivably enter the cytoplasm of their own cells and by downregulating TGFBR2, accelerate NSCLC invasion, migration and EMT while promoting NSCLC cell proliferation. Exosome analysis using clinical plasma specimens revealed that miR-20b-5p expression was considerably improved in exosomes from NSCLC patients compared with those from healthy controls. In vitro and in vivo, exosomes with high levels of miR-20b-5p were linked to the progression of NSCLC. Our data suggest that exosomes with high levels of miR-20b-5p can increase development and metastasis of NSCLC cells by downregulating TGFBR2, which would serve as a predictive and diagnostic marker for NSCLC.

Keywords: TGFBR2; epithelial‐mesenchymal transition; exosomes; miR‐20b‐5p; non‐small cell lung cancer

DOI: https://doi.org/10.1002/jbt.70080