bims-exocan 2023-11-12 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–11–12
eight papers selected by
Muhammad Rizwan, COMSATS University

Exosomal circRNA RHOT1 promotes breast cancer progression by targeting miR-204-5p/ PRMT5 axis.
Advances in the research of exosomes in renal cell carcinoma: from mechanisms to applications.
Application of exosomes as nanocarriers in cancer therapy.
Immune cell-derived exosomes as promising tools for cancer therapy.
The role of exosomes in cancer-related programmed cell death.
Extracellular Vesicles for Drug Delivery in Cancer Treatment.
Functional surfaces for exosomes capturing and exosomal microRNAs analysis.
Exosomal circCOL1A1 promotes angiogenesis via recruiting EIF4A3 protein and activating Smad2/3 pathway in colorectal cancer.

Cancer Cell Int. 2023 Nov 03. 23(1): 260

Exosomal circRNA RHOT1 promotes breast cancer progression by targeting miR-204-5p/ PRMT5 axis.

Weihua Jiang, YinPing Yu, Jianghua Ou, Yongtao Li, Ning Zhu.

   BACKGROUND: Circular RNA RHOT1 (circRHOT1) plays crucial roles in tumorigenesis by competing with microRNAs. It is largely abundant in tumor cell-derived exosomes. Meanwhile, cancer-derived exosomes participate in diverse biological processes. However, the expression patterns and functions of exosomal circRHOT1 in breast cancer remain unknown. This study is aimed to investigate and elucidate the exosomal circRHOT1/miR-204-5p/PRMT5 axis in breast cancer.
METHODS: The exosomes derived from serum samples of breast cancer patients and breast cancer cell lines were characterized using transmission electron microscopy and Western blot. MTT, colony formation, wound healing, and transwell assays were utilized to analyze cell proliferation, migration, and invasion of breast cancer cells. Flow cytometry was used for apoptosis analysis. The bioinformatics method was employed to screen differentially expressed novel circRNAs and predict the microRNA targets of circRHOT1. Dual-luciferase reporter gene assays were performed to verify their direct interaction. Finally, Xenograft experiments were used to investigate the effect of exosomal circRHOT1 on tumor growth in vivo.
RESULTS: CircRHOT1 exhibited significantly high expression in exosomes derived from the serum of breast cancer patients and breast cancer cell lines, which suggested its potential diagnostic value. Breast cancer-derived exosomes promoted the cell proliferation, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells while inhibiting apoptosis. However, exosomes with downregulated circRHOT1 inhibited the growth of co-cultured cells. Mechanistically, circRHOT1 acted as a sponge of miR-204-5p and promoted protein arginine methyltransferase 5 (PRMT5) expression. Moreover, miR-204-5p inhibitor and pcPRMT5 could reverse the tumor suppressive effects mediated by circRHOT1-knockdown. Furthermore, treatment with exosomes derived from breast cancer cells with circRHOT1 knockdown attenuated tumor growth in tumor-bearing nude mice, which was accompanied by a reduction in PRMT5 expression and an enhancement of miR-204-5p expression.
CONCLUSION: The exosomal circRHOT1 may promote breast cancer progression by regulating the miR-204-5p/PRMT5 axis. The current study strengthens the role of circRHOT1, miR-204-5p, and PRMT5 in breast cancer development and provides a potential treatment strategy for breast cancer.

Keywords:  Breast Cancer; CircRHOT1; Exosome; MiR-204-5p; PRMT5

DOI:  https://doi.org/10.1186/s12935-023-03111-5
Front Immunol. 2023 ;14 1271669

Advances in the research of exosomes in renal cell carcinoma: from mechanisms to applications.

Rui Rui, Liqun Zhou, Shiming He.

  Renal cell carcinoma (RCC) is one of the most malignant urological tumors. Currently, there is a lack of molecular markers for early diagnosis of RCC. The 5-year survival rate for early-stage RCC is generally favorable; however, the prognosis takes a significant downturn when the tumor progresses to distant metastasis. Therefore, the identification of molecular markers for RCC is crucial in enhancing early diagnosis rates. Exosomes are a type of extracellular vesicle (EV) typically ranging in size from 30 nm to 150 nm, which contain RNA, DNA, proteins, lipids, etc. They can impact neighboring receptor cells through the autocrine or paracrine pathway, influence cellular communication, and regulate the local immune cells, consequently shaping the tumor immune microenvironment and closely associating with tumor development. The clinical application of exosomes as tumor markers and therapeutic targets has ignited significant interest within the research community. This review aims to provide a comprehensive summary of the advancements in exosome research within the context of RCC.

Keywords:  extracellular vesicles; lipid biopsy; renal cell carcinoma; tumor biomarkers; tumor-derived exosomes

DOI:  https://doi.org/10.3389/fimmu.2023.1271669
J Mater Chem B. 2023 Nov 06.

Application of exosomes as nanocarriers in cancer therapy.

Jiawei Hu, Junfei Zhu, Jingjing Chai, Yudie Zhao, Jiajie Luan, Yan Wang.

Cancer remains the most common lethal disease in the world. Although the treatment choices for cancer are still limited, significant progress has been made over the past few years. By improving targeted drug therapy, drug delivery systems promoted the therapeutic effects of anti-cancer medications. Exosome is a kind of natural nanoscale delivery system with natural substance transport properties, good biocompatibility, and high tumor targeting, which shows great potential in drug carriers, thereby providing novel strategies for cancer therapy. In this review, we present the formation, distribution, and characteristics of exosomes. Besides, extraction and isolation techniques are discussed. We focus on the recent progress and application of exosomes in cancer therapy in four aspects: exosome-mediated gene therapy, chemotherapy, photothermal therapy, and combination therapy. The current challenges and future developments of exosome-mediated cancer therapy are also discussed. Finally, the latest advances in the application of exosomes as drug delivery carriers in cancer therapy are summarized, which provide practical value and guidance for the development of cancer therapy.

DOI: https://doi.org/10.1039/d3tb01991h
J Control Release. 2023 Nov 06. pii: S0168-3659(23)00720-4. [Epub ahead of print]

Immune cell-derived exosomes as promising tools for cancer therapy.

Junge Chen, Gang Zhang, Yichen Wan, Bozhang Xia, Qiankun Ni, Shaobo Shan, Zhongbo Hu, Xing-Jie Liang.

  Exosomes are nanoscale vesicles with a size of 30-150 nm secreted by living cells. They are vital players in cellular communication as they can transport proteins, nucleic acids, lipids, and etc. Immune cell-derived exosomes (imEXOs) have great potential for tumor therapy because they have many of the same functions as their parent cells. Especially, imEXOs display unique constitutive characteristics that are directly involved in tumor therapy. Herein, we begin by the biogenesis, preparation, characterization and cargo loading strategies of imEXOs. Next, we focus on therapeutic potentials of imEXOs from different kinds of immune cells against cancer from preclinical and clinical studies. Finally, we discuss advantages of engineered imEXOs and potential risks of imEXOs in cancer treatment. The advantages of engineered imEXOs are highlighted, includinhg selective killing effect, effective tumor targeting, effective lymph node targeting, immune activation and regulation, and good biosafety.

Keywords:  Cancer therapy; Immune activation and regulation; Immune cell-derived exosomes (imEXOs); Nanomedicine; Therapeutic potential

DOI:  https://doi.org/10.1016/j.jconrel.2023.11.003
Immunol Rev. 2023 Nov 10.

The role of exosomes in cancer-related programmed cell death.

Xin Li, Zuoqian Jing, Xuejie Li, Lei Liu, Xiang Xiao, Yifan Zhong, Zihan Ren.

  Cancer arises from the growth and division of uncontrolled erroneous cells. Programmed cell death (PCD), or regulated cell death (RCD), includes natural processes that eliminate damaged or abnormal cells. Dysregulation of PCD is a hallmark of cancer, as cancer cells often evade cell death and continue to proliferate. Exosomes nanoscale extracellular vesicles secreted by different types of cells carrying a variety of molecules, including nucleic acids, proteins, and lipids, to have indispensable role in the communication between cells, and can influence various cellular processes, including PCD. Exosomes have been shown to modulate PCD in cancer cells by transferring pro- or antideath molecules to neighboring cells. Additionally, exosomes can facilitate the spread of PCD to surrounding cancer cells, making them promising in the treatment of various cancers. The exosomes' diagnostic potential in cancer is also an active area of research. Exosomes can be isolated from a wide range of bodily fluids and tissues, such as blood and urine, and can provide a noninvasive way to monitor cancer progression and treatment response. Furthermore, exosomes have also been employed as a delivery system for therapeutic agents. By engineering exosomes to carry drugs or other therapeutic molecules, they can be targeted specifically to cancer cells, reducing toxicity to healthy tissues. Here, we discussed exosomes in the diagnosis and prevention of cancers, tumor immunotherapy, and drug delivery, as well as in different types of PCD.

Keywords:  cancer; diagnosis; exosome; programmed cell death; source; treatment

DOI:  https://doi.org/10.1111/imr.13286
Biol Proced Online. 2023 Nov 09. 25(1): 28

Extracellular Vesicles for Drug Delivery in Cancer Treatment.

Li Wang, Xin Yu, Juan Zhou, Chunxia Su.

  Extracellular vesicles (EVs) are nanoscale vesicles derived from cells that mediate intercellular communication by transporting bioactive molecules. They play significant roles in various physiological and pathological conditions. EVs hold great potential as novel biomarkers of diseases, therapeutic agents, and drug delivery vehicles. Furthermore, EVs as novel drug delivery vehicles have demonstrated significant advantages in preclinical settings. In this review, we discussed the biogenesis and characteristics of EVs and their functions in cancer. We summarize the therapeutic applications of EVs as a natural delivery vehicles in cancer therapy. We highlight the existing challenges, illuminate vital questions, and propose recommendations to effectively address them effectively.

Keywords:  Cancer treatment; Drug delivery; Extracellular vesicles; Natural compounds

DOI:  https://doi.org/10.1186/s12575-023-00220-3
Colloids Surf B Biointerfaces. 2023 Oct 31. pii: S0927-7765(23)00512-X. [Epub ahead of print]233 113627

Functional surfaces for exosomes capturing and exosomal microRNAs analysis.

Cristina Potrich, Anna Pedrotti, Cecilia Pederzolli, Lorenzo Lunelli.

  Exosomes are small extracellular vesicles well-studied both as cell signaling elements and as source of highly informative biomarkers, in particular microRNAs. Standard techniques for exosome isolation are in general scarcely efficient and give low purity vesicles. New techniques combining microfluidics with suitable functionalized surfaces could overcome these disadvantages. Here, different functional surfaces aimed at exosomes capture are developed thank to the functionalization of silicon oxide substrates. Charged surfaces, both positive and negative, neutral and immunoaffinity surfaces are characterized and tested in functional assays with both exosome mimicking vesicles and exosomes purified from cell supernatants. The different surfaces showed promising properties, in particular the negatively-charged surface could capture more than 4 × 108 exosomes per square centimeter. The captured exosomes could be recovered and their biomarker cargo analyzed. Exosomal microRNAs were successfully analyzed with RT-PCR, confirming the good performances of the negatively-charged surface. The best-performing functionalization could be easily moved to microdevice surfaces for developing modular microfluidic systems for on-chip isolation of exosomes, to be integrated in simple and fast biosensors aimed at biomarker analysis both in clinical settings and in research.

Keywords:  Exo-miR-21; Exosomes capture; MicroRNA; Real-time PCR; Surface functionalization

DOI:  https://doi.org/10.1016/j.colsurfb.2023.113627
Mol Med. 2023 Nov 08. 29(1): 155

Exosomal circCOL1A1 promotes angiogenesis via recruiting EIF4A3 protein and activating Smad2/3 pathway in colorectal cancer.

Gui Hu, Changwei Lin, Kai Gao, Miao Chen, Fei Long, Buning Tian.

   BACKGROUND: Colorectal cancer (CRC) is the third frequently diagnosed cancer with high incidence and mortality rate worldwide. Our previous report has demonstrated that circCOL1A1 (hsa_circ_0044556) functions as an oncogene in CRC, and Gene Ontology (GO) analysis has also revealed the strong association between circCOL1A1 and angiogenesis. However, the mechanism of circCOL1A1 or exosomal circCOL1A1 in CRC angiogenesis remains elusive.
METHODS: Purified exosomes from CRC cells were characterized by nanoparticle tracking analyzing, electron microscopy and western blot. qRT-PCR, immunohistochemistry or western blot were employed to test the expression of circCOL1A1, EIF4A3, Smad pathway and angiogenic markers. Cell proliferation of HUVECs was monitored by CCK-8 assay. The migratory and angiogenic capabilities of HUVECs were detected by wound healing and tube formation assay, respectively. Bioinformatics analysis, RNA immunoprecipitation (RIP), RNA pull-down and FISH assays were used to detect the interactions among circCOL1A1, EIF4A3 and Smad2/3 mRNA. The in vitro findings were verified in xenograft model.
RESULTS: CRC cell-derived exosomal circCOL1A1 promoted angiogenesis of HUVECs via recruiting EIF4A3. EIF4A3 was elevated in CRC tissues, and it stimulated angiogenesis of HUVECs through directly binding and stabilizing Smad2/3 mRNA. Moreover, exosomal circCOL1A1 promoted angiogenesis via inducing Smad2/3 signaling pathway in vitro, and it also accelerated tumor growth and angiogenesis in vivo.
CONCLUSION: CRC cell-derived exosomal circCOL1A1 promoted angiogenesis via recruiting EIF4A3 and activating Smad2/3 signaling.

Keywords:  Angiogenesis; CircCOL1A1; Colorectal cancer; EIF4A3; Exosomes; Smad2/3

DOI:  https://doi.org/10.1186/s10020-023-00747-x