bims-exocan 2024-03-31 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024–03–31
eleven papers selected by
Muhammad Rizwan, COMSATS University

Exploring the dynamic interplay between exosomes and the immune tumor microenvironment: implications for breast cancer progression and therapeutic strategies.
Exosomal miR-1470 is a diagnostic biomarker and promotes cell proliferation and metastasis in colorectal cancer.
Exosomal lncRNA HEIH, an essential communicator for hepatocellular carcinoma cells and macrophage M2 polarization through the miR-98-5p/STAT3 axis.
NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma.
Comprehensive Analysis of Exosomal MicroRNAs Derived from UVB-Irradiated Keratinocytes as Potential Melanogenesis Regulators.
Exosomal circ_0000735 contributes to non-small lung cancer malignant progression.
Exosomes in renal cell carcinoma: challenges and opportunities.
Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway.
Exosomal circSTRBP from cancer cells facilitates gastric cancer progression via regulating miR-1294/miR-593-3p/E2F2 axis.
Exosome-Derived MicroRNA-221-3p Desensitizes Breast Cancer Cells to Adriamycin by Regulating PIK3r1-Mediated Glycose Metabolism.
Emerging Strategies to Overcome Current CAR-T Therapy Dilemmas - Exosomes Derived from CAR-T Cells.

Breast Cancer Res. 2024 Mar 29. 26(1): 57

Exploring the dynamic interplay between exosomes and the immune tumor microenvironment: implications for breast cancer progression and therapeutic strategies.

Sahar Safaei, Manouchehr Fadaee, Omid Rahbar Farzam, Amirhossein Yari, Elham Poursaei, Cynthia Aslan, Sahar Samemaleki, Dariush Shanehbandi, Behzad Baradaran, Tohid Kazemi.

  Breast cancer continues to pose a substantial worldwide health concern, demanding a thorough comprehension of the complex interaction between cancerous cells and the immune system. Recent studies have shown the significant function of exosomes in facilitating intercellular communication and their participation in the advancement of cancer. Tumor-derived exosomes have been identified as significant regulators in the context of breast cancer, playing a crucial role in modulating immune cell activity and contributing to the advancement of the illness. This study aims to investigate the many effects of tumor-derived exosomes on immune cells in the setting of breast cancer. Specifically, we will examine their role in influencing immune cell polarization, facilitating immunological evasion, and modifying the tumor microenvironment. Furthermore, we explore the nascent domain of exosomes produced from immune cells and their prospective involvement in the prevention of breast cancer. This paper focuses on new research that emphasizes the immunomodulatory characteristics of exosomes produced from immune cells. It also explores the possibility of these exosomes as therapeutic agents or biomarkers for the early identification and prevention of breast cancer. The exploration of the reciprocal connections between exosomes formed from tumors and immune cells, together with the rising significance of exosomes derived from immune cells, presents a potential avenue for the advancement of novel approaches in the field of breast cancer therapy and prevention.

Keywords:  Breast cancer; Immune cell; Immune cell-derived exosomes; Immunotherapy; Tumor microenvironment; Tumor-derived exosomes

DOI:  https://doi.org/10.1186/s13058-024-01810-z
Cancer Med. 2024 Apr;13(7): e7117

Exosomal miR-1470 is a diagnostic biomarker and promotes cell proliferation and metastasis in colorectal cancer.

Yawen Wu, Jie Zhang, Fanfeng Lin, Yajing Zhao, Baibing Zheng, Na Zhou, Zhe Zhang, Guanghao Li, Li Xie.

   BACKGROUND: In recent years,the lack of specific markers for the diagnosis of colorectal cancer has led to an upward trend in both morbidity and mortality from this condition. There is an urgent need to identify molecular biomarkers that contribute to early cancer detection. This study aimed to identify specific exosomal microRNAs that hold potential as diagnostic biomarkers for CRC.
METHODS: We screened for differentially expressed miRNAs using the CRC exosome dataset GSE39833. To validate the results in the public database, we collected serum from 168 CRC patients and 168 healthy volunteers. The expression levels of exosomal miR-1470 in healthy volunteers and CRC patients were analyzed using qRT-PCR. To evaluate the diagnostic potential of the selected miR-1470 in distinguishing CRC patients from healthy controls, we analyzed its receiver operating characteristic curve. To explore the biological functions of miR-1470 in CRC cell lines, we detected the miR-1470's ability to regulate the growth and metastasis of CRC cells by CCK8, transwell and other assays after transfection of miR-1470 in SW480, HCT-116 cells.
RESULTS: Exosomal miR-1470 exhibited significant up-regulation in CRC patients compared to healthy volunteers. The ROC curve analysis revealed an area under the curve (AUC) of 0.74 (95% confidence interval: 0.6876-0.7920) for exosomal miR-1470, indicating its potential as a diagnostic biomarker. Furthermore, the expression level of miR-1470 in CRC patients showed correlations with age, metastasis, and HDL content. We overexpressed miR-1470 in CRC cell lines. CCK8 proliferation assay showed that miR-1470 promoted the proliferation ability of SW480 and HCT-116 cells. Transwell assay showed that miR-1470 promoted the migration and invasion ability of SW480 and HCT-116 cells.
CONCLUSION: This suggested that non-invasive diagnosis of CRC is possible by detecting the level of miR-1470 in exosomes, which has important implications for early detection and treatment of this disease.

Keywords:  colorectal cancer; diagnostic biomarkers; early detection; exosomes; miR‐1470

DOI:  https://doi.org/10.1002/cam4.7117
J Biochem Mol Toxicol. 2024 Apr;38(4): e23686

Exosomal lncRNA HEIH, an essential communicator for hepatocellular carcinoma cells and macrophage M2 polarization through the miR-98-5p/STAT3 axis.

Jun-Hua Ai, Yu-Zhong Wen, Shi-Jie Dai, Li-Dong Zhang, Zhong-Jing Huang, Jun Shi.

  Part of human long noncoding RNAs (lncRNAs) has been elucidated to play an essential role in the carcinogenesis and progression of hepatocellular carcinoma (HCC), a type of malignant tumor with poor outcomes. Tumor-derived exosomes harboring lncRNAs have also been implicated as crucial mediators to orchestrate biological functions among neighbor tumor cells. The recruitment of tumor-associated macrophages (TAMs) exerting M2-like phenotype usually indicates the poor prognosis. Yet, the precise involvement of tumor-derived lncRNAs in cross-talk with environmental macrophages has not been fully identified. In this study, we reported the aberrantly overexpressed HCC upregulated EZH2-associated lncRNA (HEIH) in tumor tissues and cell lines was positively correlated with poor prognosis, as well as enriched exosomal HEIH levels in blood plasma and cell supernatants. Besides, HCC cell-derived exosomes transported HEIH into macrophages for triggering macrophage M2 polarization, thereby in turn promoting the proliferation, migration, and invasion of HCC cells. Mechanistically, HEIH acted as a miRNA sponge for miR-98-5p to up-regulate STAT3, which was then further verified in the tumor xenograft models. Collectively, our study provides the evidence for recognizing tumor-derived exosomal lncRNA HEIH as a novel regulatory function through targeting miR-98-5p/STAT3 axis in environmental macrophages, which may shed light on the complicated tumor microenvironment among tumor and immune cells for HCC treatment.

Keywords:  STAT3; hepatocellular carcinoma; lncRNA HEIH; macrophage M2 polarization; miR‐98‐5p

DOI:  https://doi.org/10.1002/jbt.23686
Sci Rep. 2024 03 24. 14(1): 6979

NNT-AS1 in CAFs-derived exosomes promotes progression and glucose metabolism through miR-889-3p/HIF-1α in pancreatic adenocarcinoma.

Pingping Zhang, Qun Wang, Weijun Lu, Feng Zhang, Dongde Wu, Junwei Sun.

  It is metabolic and signaling crosstalk between stromal cells and tumors in the tumor microenvironment, which influences several aspects of tumor formation and drug resistance, including metabolic reprogramming. Despite considerable findings linking lncRNAs in HIF-1-related regulatory networks to cancer cell, little emphasis has been given to the role in communication between cancer-associated fibroblasts (CAFs) and tumor cells. Previously, we observed that NNT-AS1 was substantially expressed in CAFs cells and CAFs exosomes, and subsequently investigated the influence of CAFs exosomal NNT-AS1 on glucose metabolism, proliferation, and metastasis of pancreatic ductal adenocarcinoma (PDAC) cells. Transmission electron microscopy was used to examine exosomes secreted by PDAC patient-derived CAFs. qRT-PCR was used to evaluate the expression of NNT-AS1, miR-889-3p, and HIF-1. The role of CAFs-derived exosomal NNT-AS1 in PDAC cell progression and metabolism have been identified. Dual luciferase reporter assays examined the binding between NNT-AS1, miR-889-3p, and HIF-1. After PDAC cells co-culture exosomes secreted by CAFs, we found that they alter glucose metabolism, proliferation, and metastasis. In PDAC cells, CAF-derived exosomal lncRNA NNT-AS1 acted as a molecular sponge for miR-889-3p. Furthermore, HIF-1 could be targeted by miR-889-3p and was controlled by NNT-AS1. This study explores the mechanism by which NNT-AS1 influences the interaction of CAFs on glycolytic remodeling, proliferation, and metastasis of tumor cells through regulating miR-889-3p/HIF-1α, which also helps discover new clinical treatment targets for PDAC.

Keywords:  CAFs-derived exosomes; Glucose metabolism; HIF-1α; NNT-AS1; PDAC; miR-889-3p

DOI:  https://doi.org/10.1038/s41598-024-57769-6
Int J Mol Sci. 2024 Mar 07. pii: 3095. [Epub ahead of print]25(6):

Comprehensive Analysis of Exosomal MicroRNAs Derived from UVB-Irradiated Keratinocytes as Potential Melanogenesis Regulators.

Jee-Hoe Yoon, Chan-Song Jo, Jae-Sung Hwang.

  The exosomes derived from keratinocytes can have a substantial impact on melanogenesis by influencing melanocytes. MicroRNAs (miRNAs) encapsulated within exosomes are implicated in the control of melanogenesis, particularly when under the influence of UVB irradiation. This investigation explores UVB-induced exosomal miRNAs from keratinocytes as potential regulators of melanogenesis. UVB-irradiated, keratinocyte-derived exosomes were observed to augment melanogenesis in melanocytes, resulting in an upregulation of MITF, TRP1, TRP2, and TYR expression compared to non-UVB-irradiated exosomes. Additionally, a subset of exosomal miRNAs was differentially selected and confirmed to exert both enhancing and inhibitory effects on melanogenesis through functional assays. Notably, hsa-miR-644a, hsa-miR-365b-5p, and hsa-miR-29c-3p were found to upregulate melanogenesis, while hsa-miR-18a-5p, hsa-miR-197-5p, and hsa-miR-4281 downregulated melanogenesis. These findings suggest the involvement of keratinocyte-derived exosomal miRNAs in melanogenesis regulation within melanocytes. The expression levels of exosomal miRNAs from keratinocytes exhibited a UVB-dependent increase, indicating a potential role for these miRNAs as regulators of melanogenesis in response to UVB irradiation. Furthermore, melanogenesis was found to be dependent on exosomes derived from keratinocytes. This underscores the potential of UVB-induced exosomal miRNAs derived from keratinocytes as regulators of melanogenesis. Moreover, this study unveils a significant role for exosomes in melanocyte pigmentation, presenting a novel pathway in the intricate process of melanogenesis.

Keywords:  UVB; exosomes; keratinocytes; melanocytes; melanogenesis; microRNA

DOI:  https://doi.org/10.3390/ijms25063095
J Biochem Mol Toxicol. 2024 Apr;38(4): e23700

Exosomal circ_0000735 contributes to non-small lung cancer malignant progression.

Sijie Liu, Xun Wu, Yanjie Wang, Yingtai Chen.

  Circular RNA is an important regulator for non-small cell lung cancer (NSCLC). Circ_0000735 has been found to be significantly overexpressed in NSCLC tissues. Therefore, its role and mechanism in NSCLC progression need to be further explored. The expression levels of circ_0000735, miR-345-5p and A disintegrin and metalloprotease 19 (ADAM19) were determined using quantitative real-time PCR. EdU staining, wound healing and transwell assays were utilized to detect cell proliferation and metastasis. The protein levels of metastasis markers, exosome markers and ADAM19 were determined using western blot. Animal experiments were performed to confirm the role of circ_0000735 in NSCLC tumorigenesis. The exosomes from cells and serum were identified using transmission electron microscopy and nanoparticle tracking analysis. We found that circ_0000735 was upregulated in NSCLC, and its knockdown repressed NSCLC cell proliferation and metastasis. In terms of mechanism, circ_0000735 targeted miR-345-5p to regulate ADAM19. MiR-345-5p inhibitor reversed the suppressive effect of circ_0000735 knockdown on NSCLC progression, and ADAM19 overexpression abolished the inhibition effect of miR-345-5p on NSCLC progression. Also, animal experiments showed that silencing of circ_0000735 reduced NSCLC tumorigenesis. In addition, exosomes mediated the intercellular transmission of circ_0000735, and serum exosomal circ_0000735 might be an important indicator for the diagnosis of NSCLC. In conclusion, circ_0000735 facilitated NSCLC progression via miR-345-5p/ADAM19 pathway, and serum exosomal circ_0000735 might be a potential biomarker for NSCLC diagnosis.

Keywords:  ADAM19; NSCLC; circ_0000735; exosome; miR‐345‐5p

DOI:  https://doi.org/10.1002/jbt.23700
Mol Biol Rep. 2024 Mar 23. 51(1): 443

Exosomes in renal cell carcinoma: challenges and opportunities.

Mahan Mohammadi, Kamran Mansouri, Pantea Mohammadi, Mehran Pournazari, Houshang Najafi.

  Renal cell carcinoma (RCC) is the most common type of kidney cancer that accounts for approximately 2-3% of adult malignancies. Among the primary treatment methods for this type of cancer are surgery and targeted treatment. Still, due to less than optimal effectiveness, there are problems such as advanced distant metastasis, delayed diagnosis, and drug resistance that continue to plague patients. In recent years, therapeutic advances have increased life expectancy and effective treatment in renal cell carcinoma patients. One of these methods is the use of stem cells. Although the therapeutic effects of stem cells, especially mesenchymal stem cells, are still impressive, today, extracellular vesicles (EVs) as carrying molecules and various mediators in intercellular communications, having a central role in tumorigenesis, metastasis, immune evasion, and drug response, and on the other hand, due to its low immunogenicity and strong regulatory properties of the immune system, has received much attention from researchers and doctors. Despite the increasing interest in exosomes as the most versatile type of EVs, the heterogeneity of their efficacy presents challenges and, on the other hand, exciting opportunities for diagnostic and clinical interventions.In the upcoming article, we will review the various aspects of exosomes' effects in the prevention, treatment, and progress of renal cell carcinoma and also ways to optimize them to strengthen their positive sides.

Keywords:  Exosome; Regenerative medicine; Renal cell carcinoma; Stem cell

DOI:  https://doi.org/10.1007/s11033-024-09384-x
Mol Cancer. 2024 Mar 27. 23(1): 65

Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway.

Zhiqiang He, Yuhan Zhong, Parbatraj Regmi, Tianrun Lv, Wenjie Ma, Junke Wang, Fei Liu, Siqi Yang, Yanjie Zhong, Rongxing Zhou, Yanwen Jin, Nansheng Cheng, Yujun Shi, Haijie Hu, Fuyu Li.

   BACKGROUND: Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking.
METHODS: LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1.
RESULTS: TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect.
CONCLUSIONS: TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.

Keywords:  Angiogenesis; Exosome; Gallbladder cancer; IGF2BP2; NOTCH1; PABPC1; TRPM2-AS

DOI:  https://doi.org/10.1186/s12943-024-01979-z
J Cell Mol Med. 2024 Apr;28(8): e18217

Exosomal circSTRBP from cancer cells facilitates gastric cancer progression via regulating miR-1294/miR-593-3p/E2F2 axis.

Yin Wang, Rong Zou, Deke Li, Xiankui Gao, Xingjun Lu.

  CircRNAs represent a new class of non-coding RNAs which show aberrant expression in diverse cancers, such as gastric cancer (GC). circSTRBP, for instance, is suggested to be overexpressed in GC cells and tissues. However, the biological role of circSTRBP in the progression of GC and the potential mechanisms have not been investigated. circSTRBP levels within GC cells and tissues were measured by RT-qPCR. The stability of circSTRBP was assessed by actinomycin D and Ribonuclease R treatment. Cell proliferation, migration, invasion and in vitro angiogenic abilities after circSTRBP knockdown were analysed through CCK-8 assay, transwell culture system and the tube formation assay. The interaction of circSTRBP with the predicted target microRNA (miRNA) was examined by RNA immunoprecipitation and luciferase reporter assays. Xenograft tumour model was established to evaluate the role of exosomal circSTRBP in the tumour formation of GC cells. circSTRBP was upregulated in GC cells and tissues, and there was an increased level of circSTRBP in GC-derived exosomes. circSTRBP in the exosomes enhanced GC cell growth and migration in vitro, which modulates E2F Transcription Factor 2 (E2F2) expression through targeting miR-1294 and miR-593-3p. Additionally, exosomal circSTRBP promoted the tumour growth of GC cells in the xenograft model. Exosomal circSTRBP is implicated in the progression of GC by modulating the activity of miR-1294/miR-593-3p/E2F2 axis.

Keywords:  E2F2 by modulating; circRNA; circSTRBP; exosome; gastric cancer; miRNA

DOI:  https://doi.org/10.1111/jcmm.18217
Cancer Biother Radiopharm. 2024 Mar 26.

Exosome-Derived MicroRNA-221-3p Desensitizes Breast Cancer Cells to Adriamycin by Regulating PIK3r1-Mediated Glycose Metabolism.

Xiaolu Hong, Xiaoping Pan.

  Background: Cancer-derived exosomes facilitate chemoresistance by transferring RNAs, yet their role in exosomal microRNA-221-3p (miR-221-3p) regulation of Adriamycin resistance in breast cancer (BC) remains unclear. Methods: Adriamycin-resistant BC cells were developed from MCF-7 and MDA-MB-231 cells by incremental Adriamycin exposure. The miR-221-3p levels were quantified by quantitative reverse transcription-polymerase chain reaction. Subsequently, exosomes were isolated and incubated with BC cells, and exosome-mediated Adriamycin sensitivity was evaluated using Cell Counting Kit-8, colony formation, and flow cytometry assays. Sensitive cells were cocultured with miR-221-3p inhibitor-treated cells to assess Adriamycin resistance. Moreover, the interaction between miR-221-3p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) was validated using a dual luciferase reporter gene assay. Mimics and inhibitors were used to determine the effects of miR-221-3p on Adriamycin resistance. Results: Elevated levels of miR-221-3p expression were observed in Adriamycin-resistant BC cells and exosomes. Sensitive cells were cocultured with exosomes from resistant cells, resulting in increased half-maximal inhibitory concentration value and proliferation, and reduced Adriamycin-induced apoptosis. However, the effects of coculturing sensitive cells with Adriamycin-resistant cells were significantly weakened by miR-221-3p inhibitor transfection in Adriamycin-resistant cells. PIK3R1 was found to be a target of miR-221-3p, and miR-221-3p mimics enhanced Adriamycin resistance in sensitive cells. miR-221-3p inhibitors increased the expression of PIK3R1, p-AKT, c-Myc, HK2, and PKM2, decreased FOXO3 expression, and weakened the Adriamycin resistance in resistant cells. Conclusions: miR-221-3p can be transferred between BC cells through exosomes. High levels of miR-221-3p were found to target PIK3R1 and promoted Adriamycin resistance in BC cells. [Figure: see text].

Keywords:  Adriamycin resistance; PIK3R1; breast cancer; exosome; glucose metabolism; miR-221-3p

DOI:  https://doi.org/10.1089/cbr.2023.0123
Int J Nanomedicine. 2024 ;19 2773-2791

Emerging Strategies to Overcome Current CAR-T Therapy Dilemmas - Exosomes Derived from CAR-T Cells.

Dong Hu, Ruyue Yang, Guidan Wang, Hao Li, Xulong Fan, Gaofeng Liang.

  Adoptive T cells immunotherapy, specifically chimeric antigen receptor T cells (CAR-T), has shown promising therapeutic efficacy in the treatment of hematologic malignancies. As extensive research on CAR-T therapies has been conducted, various challenges have emerged that significantly hampered their clinical application, including tumor recurrence, CAR-T cell exhaustion, and cytokine release syndrome (CRS). To overcome the hurdles of CAR-T therapy in clinical treatment, cell-free emerging therapies based on exosomes derived from CAR-T cells have been developed as an effective and promising alternative approach. In this review, we present CAR-T cell-based therapies for the treatment of tumors, including the features and benefits of CAR-T therapies, the limitations that exist in this field, and the measures taken to overcome them. Furthermore, we discuss the notable benefits of utilizing exosomes released from CAR-T cells in tumor treatment and anticipate potential issues in clinical trials. Lastly, drawing from previous research on exosomes from CAR-T cells and the characteristics of exosomes, we propose strategies to overcome these restrictions. Additionally, the review discusses the plight in large-scale preparation of exosome and provides potential solutions for future clinical applications.

Keywords:  CAR-T cells; exosome; immune escape; tumor

DOI:  https://doi.org/10.2147/IJN.S445101