bims-exocan 2023-02-19 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–02–19
sixteen papers selected by
Muhammad Rizwan, COMSATS University

Evaluating tumor cell- and T cell-derived extracellular vesicles as potential biomarkers of cancer and immune cell competence.
Exosomal circTUBGCP4 promotes vascular endothelial cell tipping and colorectal cancer metastasis by activating Akt signaling pathway.
Hypoxic glioma cell-secreted exosomal circ101491 promotes the progression of glioma by regulating miR-125b-5p/EDN1.
Exosomes derived from hypoxic glioma deliver miR-1246 and miR-10b-5p to normoxic glioma cells to promote migration and invasion.
Propofol mediates bone metastasis by regulating PC-derived exosomal miR-142-3p.
Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis.
Effect of the Application of Exosome on Gastric Cancer.
Exosomal miRNA in early-stage hepatocellular carcinoma.
Tumor-derived extracellular vesicles hybridized liposomes in cancer therapy.
Magnetic-nanowaxberry-based microfluidic ExoSIC for affinity and continuous separation of circulating exosomes towards cancer diagnosis.
Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages.
Early Cancer Biomarker Discovery Using DIA-MS Proteomic Analysis of EVs from Peripheral Blood.
Recent advancements to engineer mesenchymal stem cells and their extracellular vesicles for targeting and destroying tumors.
Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway.
Effect of Exosomal lncRNA MALAT1/miR-370-3p/STAT3 Positive Feedback Loop on PI3K/Akt Pathway Mediating Cisplatin Resistance in Cervical Cancer Cells.
Extracellular Vesicles as Next Generation Immunotherapeutics.

Expert Rev Mol Diagn. 2023 Feb 14.

Evaluating tumor cell- and T cell-derived extracellular vesicles as potential biomarkers of cancer and immune cell competence.

Theresa L Whiteside.

   INTRODUCTION: Extracellular vesicles (EVs) produced by tumors, also called tumor-derived exosomes (TEX), have been implicated in inducing immune cell suppression in vitro and in vivo. The development of a novel category of noninvasive biomarkers for precision oncology remains an unmet need, and TEX emerge as a promising liquid tumor biopsy component.
AREAS COVERED: TEX play a critical role in monitoring cancer presence/progression and in reprograming of anti-tumor effector T cells to producers of EVs with pro-tumor activity. TEX are a subset of circulating EVs. Their separation by immune capture from EVs derived from non-malignant cells allows for TEX phenotypic/functional assessments. TEX cross-talking with CD3(+) T cells induce the release of CD3(+) small EV (sEV), whose cargo of suppressor proteins resembles that of TEX and further contributes to cancer-induced immune suppression. While TEX recapitulate the genetic/molecular phenotype of tumor cells, CD3(+) sEV might serve as "T cell liquid biopsy".
EXPERT OPINION: Pre-clinical explorations of the role in cancer body fluids of TEX and CD3(+) sEV as cancer biomarkers suggest that these EV subsets may qualify as liquid tumor biopsy noninvasive components in the near future. Their potential to simultaneously serve as noninvasive liquid tumor biopsy and T cell biopsy remains to be validated in future clinical trials.

Keywords:  CD3(+) small EV; Extracellular vesicles (EVs); T cell liquid biopsy; TEX-reprogrammed T cells; cancer; tumor-derived exosomes (TEX)

DOI:  https://doi.org/10.1080/14737159.2023.2178902
J Exp Clin Cancer Res. 2023 Feb 15. 42(1): 46

Exosomal circTUBGCP4 promotes vascular endothelial cell tipping and colorectal cancer metastasis by activating Akt signaling pathway.

Chen Chen, Yang Liu, Lin Liu, Chaohua Si, Yanxin Xu, Xiaoke Wu, Chengzeng Wang, Zhenqiang Sun, Qiaozhen Kang.

   BACKGROUND: Exosome is crucial mediator and play an important role in tumor angiogenesis. Tip cell formation is a prerequisite for persistent tumor angiogenesis which causes tumor metastasis. However, the functions and underlying mechanisms of tumor cell-derived exosomes in angiogenesis and tip cell formation remain less understood.
METHODS: Exosomes derived from serum of colorectal cancer (CRC) patients with metastasis/non-metastasis and CRC cells were isolated by ultracentrifugation. CircRNAs in these exosomes were analyzed by circRNA microarray. Then, exosomal circTUBGCP4 was identified and verified by quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Loss- and gain-of-function assays were performed to explore the effect of exosomal circTUBGCP4 on vascular endothelial cell tipping and colorectal cancer metastasis in vitro and in vivo. Mechanically, bioinformatics analysis, biotin-labeled circTUBGCP4/ miR-146b-3p RNA pulldown, RNA immunoprecipitation (RIP), and luciferase reporter assay were used to confirm the interaction among circTUBGCP4, miR-146b-3p, and PDK2.
RESULTS: Here, we showed that exosomes derived from CRC cells enhanced vascular endothelial cell migration and tube formation via inducing filopodia formation and endothelial cell tipping. We further screened the upregulated circTUBGCP4 in serum of CRC patients with metastasis compared to non-metastasis. Silencing circTUBGCP4 expression in CRC cell-derived exosomes (CRC-CDEs) inhibited endothelial cell migration, tube formation, tip cell formation, and CRC metastasis. Overexpression of circTUBGCP4 had opposite results in vitro and in vivo. Mechanically, circTUBGCP4 upregulated PDK2 to activate Akt signaling pathway by sponging miR-146b-3p. Moreover, we found that miR-146b-3p could be a key regulator for vascular endothelial cell dysfunction. Exosomal circTUBGCP4 promoted tip cell formation and activated the Akt signaling pathway by inhibiting miR-146b-3p.
CONCLUSIONS: Our results suggest that colorectal cancer cells generate exosomal circTUBGCP4, which causes vascular endothelial cell tipping to promote angiogenesis and tumor metastasis by activating Akt signaling pathway.

Keywords:  Angiogenesis; CircRNA; Exosome; Tip cells formation; Tumor metastasis

DOI:  https://doi.org/10.1186/s13046-023-02619-y
Brain Res Bull. 2023 Feb 14. pii: S0361-9230(23)00036-9. [Epub ahead of print]

Hypoxic glioma cell-secreted exosomal circ101491 promotes the progression of glioma by regulating miR-125b-5p/EDN1.

Xiao-Hui Zhang, Yi-Cun Song, Feng Qiu, Zheng-Cai Wang, Nan Li, Fang-Bo Zhao.

  Hypoxia and exosomes play important roles in the occurrence and development of glioma. While circRNAs are involved in biological processes of various tumors, the mechanism underlying exosome-dependent regulatory effects of circRNAs on the progression of glioma under hypoxia is unclear. Results suggested that circ101491 was overexpressed in tumor tissues and plasma exosomes of glioma patients, while the overexpression of circ101491 was closely related to the differentiation degree and TNM staging of the patients. Moreover, circ101491 overexpression promoted viability, invasion and migration of glioma cells both in vivo and in vitro; the above regulatory effects can be reversed by inhibition of circ101491 expression. Mechanistic studies revealed that circ101491 upregulated EDN1 expression through sponging miR-125b-5p, thus facilitating glioma progression. In summary, hypoxia could promote circ101491 overexpression in glioma cell-derived exosomes, and circ101491/miR-125b-5p/EDN1 regulatory axis might be implicated in the malignant progression of glioma.

Keywords:  Glioma; circ101491; exosomes; hypoxia; miR-125b-5p

DOI:  https://doi.org/10.1016/j.brainresbull.2023.02.006
Lab Invest. 2021 May;pii: S0023-6837(22)00640-7. [Epub ahead of print]101(5): 612-624

Exosomes derived from hypoxic glioma deliver miR-1246 and miR-10b-5p to normoxic glioma cells to promote migration and invasion.

Mingyu Qian, Zihang Chen, Xiaofan Guo, Shaobo Wang, Zongpu Zhang, Wei Qiu, Yanhua Qi, Shouji Zhang, Jianye Xu, Rongrong Zhao, Hao Xue, Gang Li.

Hypoxia is an important feature of the tumor microenvironment and is associated with glioma progression and patient outcome. Exosomes have been implicated in the intercellular communication in the tumor microenvironment. However, the effects of hypoxic glioma exosomes on glioma migration and invasion and the underlying mechanisms remain poorly understood. In this study, we found that exosomes derived from hypoxic glioma cells (H-GDEs) promoted normoxic glioma migration and invasion in vitro and in vivo. Given that exosomes can regulate recipient cell functions by delivering microRNAs, we further revealed miR-1246 and miR-10b-5p were upregulated significantly in H-GDEs and delivered to normoxic glioma cells by H-GDEs. Moreover, we determined the clinical relevance of miR-1246 and miR-10b-5p in glioma patients. Subsequent investigations indicated that miR-1246 and miR-10b-5p markedly induced glioma migration and invasion in vitro and in vivo. Finally, we demonstrated that miR-1246 and miR-10b-5p induced glioma migration and invasion by directly targeting FRK and TFAP2A respectively. In conclusion, our findings suggest that the hypoxic microenvironment stimulates glioma to generate miR-1246- and miR-10b-5p-rich exosomes that are delivered to normoxic glioma cells to promote their migration and invasion; treatment targeting miR-1246 and miR-10b-5p may impair the motility of gliomas, providing a novel direction for the development of antitumor therapy.

DOI: https://doi.org/10.1038/s41374-020-00522-0
Bull Cancer. 2023 Feb 11. pii: S0007-4551(23)00049-8. [Epub ahead of print]

Propofol mediates bone metastasis by regulating PC-derived exosomal miR-142-3p.

Nianping Chen, Jiang Qian, Dan Wu, Wei Chen, Jiayan Mao, Ying Cai, Mengting Gu.

  In this study we investigated the role of propofol in mediating prostate cancer (PCa) bone metastasis through regulating exosomal factors derived from PCa. We isolated exosomes from PCa cells and co-cultured them with mesenchymal stem cells (MSCs). PCa-derived exosomes increased calcium deposition of MSCs and upregulated ALPL'Alkaline phosphatase, tissue-nonspecific isozyme) and BGLAP (Bone Gamma-Carboxyglutamate Protein) expression. Propofol treatment reduced alkaline phosphatase (ALP) activity, and ALPL and BGLAP expression that was induced by PCa-derived exosomes in MSCs. miRNAs present in cancer cell-derived exosomes increased osteogenesis in these cells. We evaluated miRNA expression in PCa cells after treatment with propofol, and found that miR-142-3p was upregulated in PCa cells. Furthermore, we transfected MSCs with miR-142-3p mimics or inhibitors and revealed that miR-142-3p mimics reduced calcium deposition and downregulated ALP activity, and ALPL and BGLAP levels, while miR-142-3p inhibitors increased calcium deposition and increased ALP activity, and ALPL and BGLAP levels. Finally, we determined that MSCs co-cultured with PCa-derived exosomes and transfected with miR-142-3p mimic exhibited reduced calcium deposition and lower ALP activity, and expression of ALPL and BGLAP. These data demonstrate that propofol inhibits osteogenic differentiation and mineralization of MSCs induced by PCa-derived exosomes by regulation of miR-142-3p levels.

Keywords:  Bone metastasis; Exosome; Propofol; Prostate cancer; miR-142-3p

DOI:  https://doi.org/10.1016/j.bulcan.2023.01.008
Mol Cancer. 2023 Feb 16. 22(1): 33

Recent advances of small extracellular vesicle biomarkers in breast cancer diagnosis and prognosis.

Yujin Lee, Jie Ni, Julia Beretov, Valerie C Wasinger, Peter Graham, Yong Li.

  Current clinical tools for breast cancer (BC) diagnosis are insufficient but liquid biopsy of different bodily fluids has recently emerged as a minimally invasive strategy that provides a real-time snapshot of tumour biomarkers for early diagnosis, active surveillance of progression, and post-treatment recurrence. Extracellular vesicles (EVs) are nano-sized membranous structures 50-1000 nm in diameter that are released by cells into biological fluids. EVs contain proteins, nucleic acids, and lipids which play pivotal roles in tumourigenesis and metastasis through cell-to-cell communication. Proteins and miRNAs from small EVs (sEV), which range in size from 50-150 nm, are being investigated as a potential source for novel BC biomarkers using mass spectrometry-based proteomics and next-generation sequencing. This review covers recent developments in sEV isolation and single sEV analysis technologies and summarises the sEV protein and miRNA biomarkers identified for BC diagnosis, prognosis, and chemoresistance. The limitations of current sEV biomarker research are discussed along with future perspective applications.

Keywords:  Biomarker; Breast cancer; Diagnosis; Extracellular vesicles; Liquid biopsy; Prognosis

DOI:  https://doi.org/10.1186/s12943-023-01741-x
Comb Chem High Throughput Screen. 2023 Feb 13.

Effect of the Application of Exosome on Gastric Cancer.

Jing Peng, Yiwen Wu, Sijun Deng, Pu Cao, Wei Yang, Tingyi Gong, Xiaoyong Lei, Xiaoyan Yang.

  Gastric cancer is one of the most common and highest mortality rate cancers in the world. Exosomes are vesicles secreted by cells carrying a large amount of information such as protein and RNA. Numerous studies have confirmed that exosomes are involved in various stages of the occurrence and development of gastric cancer and play an important role.With the gradual development, exosomes are widely developed in the diagnosis and treatment of gastric cancer. In this review, we made a basic overview of exosome, and discussed the role of exosome in the occurrence, proliferation, invasion, metastasis and drug resistance of gastric cancer. In addition, we emphasized the powerful effect and bright development prospect of exosome in the diagnosis and treatment of gastric cancer. The data of the discovery, diagnosis, treatment and prognosis of gastric cancer are not particularly optimistic, but the discovery of exosome, applied in diagnosis and treatment, provides a new and effective way to improve the survival rate of patients with gastric cancer.

Keywords:  Exosome; diagnosis; gastric cancer; physiological function; prognosis; treatment

DOI:  https://doi.org/10.2174/1386207326666230213141627
World J Clin Cases. 2023 Jan 26. 11(3): 528-533

Exosomal miRNA in early-stage hepatocellular carcinoma.

Zhi-Qiang Wu, Yi-Xin Zhu, Yun Jin, Yin-Chu Zhan.

  The incidence and mortality of hepatic carcinoma (HCC) remain high, and early diagnosis of HCC is seen as a key approach in improving clinical outcomes. However, the sensitivity and specificity of current early screening methods for HCC are not satisfactory. In recent years, research around exosomal miRNA has gradually increased, and these molecules have emerged as attractive candidates for early diagnosis and treatment of HCC. This review summarizes the feasibility of using miRNAs in peripheral blood exosomes as early diagnostic tools for HCC.

Keywords:  Biomarker; Early diagnosis; Exosomal miRNA; Hepatic carcinoma

DOI:  https://doi.org/10.12998/wjcc.v11.i3.528
Biophys J. 2023 Feb 10. pii: S0006-3495(22)03366-5. [Epub ahead of print]122(3S1): 455a-456a

Tumor-derived extracellular vesicles hybridized liposomes in cancer therapy.

Shoukath Sulthana, Santosh Aryal.

DOI: https://doi.org/10.1016/j.bpj.2022.11.2450
Lab Chip. 2023 Feb 15.

Magnetic-nanowaxberry-based microfluidic ExoSIC for affinity and continuous separation of circulating exosomes towards cancer diagnosis.

Lihua Ding, Xia Liu, Zhenzhong Zhang, Li-E Liu, Sitian He, Yan Wu, Clement Yaw Effah, Ruiying Yang, Aiai Zhang, Wensi Chen, Mubarak Yarmamat, Lingbo Qu, Xiaonan Yang, Yongjun Wu.

Exosomes are seen as promising biomarkers for minimally invasive liquid biopsies and disease surveillance. However, the complexity of body fluids, inherent heterogeneity, and tiny size of exosomes impede their extraction, consequently restricting their clinical application. In this study, in order to efficiently isolate exosomes from clinical samples, an irregular serpentine channel microfluidic chip (ExoSIC) was designed to continuously separate exosomes from plasma based on a magnetic-nanowaxberry (MNWB). In the ExoSIC, irregular serpentine microchannels are utilized to increase fluid chaotic mixing, hence improving exosome capture efficiency. In comparison to commonly used spherical magnetic particles, the designed MNWB can not only enhance the capture efficiency of exosomes, but also possess a size-exclusion effect to improve exosome purity. Consequently, the ExoSIC exhibited a large yield (24 times higher than differential centrifugation), optimum purity (greater than precipitation and similar to differential centrifugation), and high specificity. Furthermore, the ExoSIC was utilized for plasma-based cancer diagnosis by multiplex monitoring of five exosomal biomarkers (exosomal concentration, EGFR, EpCAM, SAA1 and FV), and the AUC reached 0.791. This work provides a comprehensive framework for exosome-based cancer diagnostics in order to meet clinical requirements for exosome isolation and downstream analysis.

DOI: https://doi.org/10.1039/d2lc00996j
J Exp Clin Cancer Res. 2023 Feb 17. 42(1): 48

Targeting tumor exosomal circular RNA cSERPINE2 suppresses breast cancer progression by modulating MALT1-NF-𝜅B-IL-6 axis of tumor-associated macrophages.

Boxuan Zhou, Zhaohong Mo, Guie Lai, Xiaohong Chen, Ruixi Li, Runxin Wu, Jia Zhu, Fang Zheng.

   BACKGROUND: Circular RNAs (circRNAs) have important regulatory functions in cancer, but the role of circRNAs in the tumor microenvironment (TME) remains unclear. Moreover, we also explore the effects of si-circRNAs loaded in nanoparticles as therapeutic agent for anti-tumor in vivo.
METHODS: We conducted bioinformatics analysis, qRT-PCR, EdU assays, Transwell assays, co-culture system and multiple orthotopic xenograft models to investigate the expression and function of circRNAs. Additionally, PLGA-based nanoparticles loaded with si-circRNAs were used to evaluate the potential of nanotherapeutic strategy in anti-tumor response.
RESULTS: We identified oncogene SERPINE2 derived circRNA, named as cSERPINE2, which was notably elevated in breast cancer and was closely related to poor clinical outcome. Functionally, tumor exosomal cSERPINE2 was shuttled to tumor associated macrophages (TAMs) and enhanced the secretion of Interleukin-6 (IL-6), leading to increased proliferation and invasion of breast cancer cells. Furthermore, IL-6 in turn increased the EIF4A3 and CCL2 levels within tumor cells in a positive feedback mechanism, further enhancing tumor cSERPINE2 biogenesis and promoting the recruitment of TAMs. More importantly, we developed a PLGA-based nanoparticle loaded with si-cSERPINE2, which effectively attenuated breast cancer progression in vivo.
CONCLUSIONS: Our study illustrates a novel mechanism that tumor exosomal cSERPINE2 mediates a positive feedback loop between tumor cells and TAMs to promote cancer progression, which may serve as a promising nanotherapeutic strategy for the treatment of breast cancer.

Keywords:  Breast cancer; Exosome; Nanoparticles; Tumor-associated macrophages; cSERPINE2

DOI:  https://doi.org/10.1186/s13046-023-02620-5
Methods Mol Biol. 2023 ;2628 127-152

Early Cancer Biomarker Discovery Using DIA-MS Proteomic Analysis of EVs from Peripheral Blood.

Camila Espejo, Bruce Lyons, Gregory M Woods, Richard Wilson.

  One of the cornerstones of effective cancer treatment is early diagnosis. In this context, the identification of proteins that can serve as cancer biomarkers in bodily fluids ("liquid biopsies") has gained attention over the last decade. Plasma and serum fractions of blood are the most commonly investigated sources of potential cancer liquid biopsy biomarkers. However, the high complexity and dynamic range typical of these fluids hinders the sensitivity of protein detection by the most commonly used mass spectrometry technology (data-dependent acquisition mass spectrometry (DDA-MS)). Recently, data-independent acquisition mass spectrometry (DIA-MS) techniques have overcome the limitations of DDA-MS, increasing sensitivity and proteome coverage. In addition to DIA-MS, isolating extracellular vesicles (EVs) can help to increase the depth of serum/plasma proteome coverage by improving the identification of low-abundance proteins which are a potential treasure trove of diagnostic molecules. EVs, the nano-sized membrane-enclosed vesicles present in most bodily fluids, contain proteins which may serve as potential biomarkers for various cancers. Here, we describe a detailed protocol that combines DIA-MS and EV methodologies for discovering and validating early cancer biomarkers using blood serum. The pipeline includes size exclusion chromatography methods to isolate serum-derived extracellular vesicles and subsequent EV sample preparation for liquid chromatography and mass spectrometry analysis. Procedures for spectral library generation by DDA-MS incorporate methods for off-line peptide separation by microflow HPLC with automated fraction concatenation. Analysis of the samples by DIA-MS includes recommended protocols for data processing and statistical methods. This pipeline will provide a guide to discovering and validating EV-associated proteins that can serve as sensitive and specific biomarkers for early cancer detection and other diseases.

Keywords:  Biomarker; Blood; Cancer early diagnostic; Data-independent acquisition; Extracellular vesicles; Proteomics

DOI:  https://doi.org/10.1007/978-1-0716-2978-9_9
Prog Biophys Mol Biol. 2023 Feb 11. pii: S0079-6107(23)00013-5. [Epub ahead of print]178 1-16

Recent advancements to engineer mesenchymal stem cells and their extracellular vesicles for targeting and destroying tumors.

Mohsen Karami Fath, Zahra Moayedi Banan, Reza Barati, Omid Mohammadrezakhani, Aliasghar Ghaderi, Ali Hatami, Shamim Ghiabi, Nazanin Zeidi, Katayoon Asgari, Zahra Payandeh, Ghasem Barati.

  Mesenchymal stem cells (MSCs) have the ability to migrate into tumor sites and release growth factors to modulate the tumor microenvironment. MSC therapy have shown a dual role in cancers, promoting or inhibiting. However, MSCs could be used as a carrier of anticancer agents for targeted tumor therapy. Recent technical improvements also allow engineering MSCs to improve tumor-targeting properties, protect anticancer agents, and decrease the cytotoxicity of drugs. While some of MSC functions are mediated through their secretome, MSCs-derived extracellular vesicles (EVs) are also proposed as a possible viechle for cancer therapy. EVs allow efficient loading of anticancer agents and have an intrinsic ability to target tumor cells, making them suitable for targeted therapy of tumors. In addition, the specificity and selectivity of EVs to the tumor sites could be enhanced by surface modification. In this review, we addressed the current approaches used for engineering MSCs and EVs to effectively target tumor sites and deliver anticancer agents.

Keywords:  Extracellular vesicles; Genetically engineered MSCs; Mesenchymal stem cells; Oncolytic virotherapy; Targeted tumor therapy

DOI:  https://doi.org/10.1016/j.pbiomolbio.2023.02.001
Mol Med Rep. 2023 Mar;pii: 72. [Epub ahead of print]27(3):

Effect of miR‑29a‑3p in exosomes on glioma cells by regulating the PI3K/AKT/HIF‑1α pathway.

Zeqiang Liu, Zheng Yang, Lu He.

  Exosomes secreted by glioma cells can carry a number of bioactive molecules. As the most abundant noncoding RNA in exosomes, microRNAs (miRNAs) are involved in signaling between tumor cells in a number of ways. In addition, hypoxia is an important feature of the microenvironment of most tumors. The present study investigated the effect of miR‑29a‑3p in glioma exosomes on the proliferation and apoptosis levels of U251 glioma cells under hypoxia. Qualitative PCR results showed that the expression level of miR‑29a‑3p in plasma exosomes of glioma patients was lower than that of normal subjects. By conducting hypoxia experiments in vitro on U251 glioma cells, it was found that the expression level of miR‑29a‑3p decreased following hypoxia, while overexpression of miR‑29a‑3p significantly decreased the proliferation of U251 glioma cells and promoted apoptosis by inhibiting the expression of the antiapoptotic marker Bcl‑2 and increasing the expression of the proapoptotic marker Bax The potential targets of miR‑29a‑3p were predicted by online tools and validated by a dual‑luciferase gene reporter assay. miR‑29a‑3p was found to target and regulate PI3K, which in turn inhibited the activity of the PI3K‑AKT pathway, thereby reducing the expression of hypoxia inducible factor (HIF)‑1α protein. Furthermore, the effects of miR‑29a‑3p on proliferation and apoptosis in glioma cells in those processes could be reversed by the PI3K‑AKT agonist Recilisib. In addition, the inhibitory effect of miR‑29a‑3p on the PI3K/AKT/HIF‑1α regulatory axis could cause a decrease in the expression levels of pyruvate dehydrogenase kinase‑1 and pyruvate dehydrogenase kinase‑2 and eventually lead to a reduction in glycolysis in U251 glioma cells. Similarly, Recilisib slowed the inhibitory effect of miR‑29a‑3p on glycolysis and glycolysis‑related molecules. The results of this study tentatively confirm that miR‑29a‑3p carried by exosomes can be used as a novel diagnostic marker and a potential inhibitory molecule for glioma cells, providing a new theoretical and experimental basis for the precise clinical treatment of glioma.

Keywords:  exosome; glioma; hypoxia inducible factor 1α; microRNA 29a‑3p

DOI:  https://doi.org/10.3892/mmr.2023.12959
J Oncol. 2023 ;2023 6341011

Effect of Exosomal lncRNA MALAT1/miR-370-3p/STAT3 Positive Feedback Loop on PI3K/Akt Pathway Mediating Cisplatin Resistance in Cervical Cancer Cells.

Yi Hu, Genlin Li, Yan Ma, Guifang Luo, Qian Wang, Shufen Zhang.

Background: Exosomes can encapsulate lncRNA to mediate intercellular communication in cancer progression. Our study devoted to research the effect that long noncoding RNA Metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) influence on cervical cancer (CC).
Methods: MALAT1 and miR-370-3p levels in CC was assessed using qRT-PCR. CCK-8 assay and flow cytometry were devoted to confirm the influence on MALAT1 influencing the proliferation in cisplatin-resistant CC cells. Futher more, MALAT1, combined with miR-370-3p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay.
Results: In CC tissues, MALAT1 turned into substantially expressed, cisplatin-resistant cell lines, as well as exosomes. Cell proliferation was restrained and cisplatin-induced apoptosis was promoted by way of Knockout MALAT1. And promoted the miR-370-3p level, MALAT1 targeted miR-370-3p. Promoting effect of MALAT1 on cisplatin resistance of CC was partially reversed through miR-370-3p. In addition, STAT3 may induce up-regulation of MALAT1 expression in cisplatin-resistant CC cells. It was further confirmed that the effect of MALAT1 on cisplatin-resistant CC cells was achieved by activating PI3K/Akt pathway.
Conclusion: The positive feedback loop of exosomal MALAT1/miR-370-3p/STAT3 mediates the cisplatin resistance of cervical cancer cells affecting PI3K/Akt pathway. Exosomal MALAT1 may become a promising therapeutic target for treating cervical cancer.

DOI: https://doi.org/10.1155/2023/6341011
Semin Cancer Biol. 2023 Feb 09. pii: S1044-579X(23)00017-2. [Epub ahead of print]

Extracellular Vesicles as Next Generation Immunotherapeutics.

David W Greening, Rong Xu, Anukreity Ale, Christoph E Hagemeyer, Weisan Chen.

  Extracellular vesicles (EVs) function as a mode of intercellular communication and molecular transfer to elicit diverse biological/functional response. Accumulating evidence has highlighted that EVs from immune, tumour, stromal cells and even bacteria and parasites mediate the communication of various immune cell types to dynamically regulate host immune response. EVs have an innate capacity to evade recognition, transport and transfer functional components to target cells, with subsequent removal by the immune system, where the immunological activities of EVs impact immunoregulation including modulation of antigen presentation and cross-dressing, immune activation, immune suppression, and immune surveillance, impacting the tumour immune microenvironment. In this review, we outline the recent progress of EVs in immunorecognition and therapeutic intervention in cancer, including vaccine and targeted drug delivery and summarise their utility towards clinical translation. We highlight the strategies where EVs (natural and engineered) are being employed as a therapeutic approach for immunogenicity, tumoricidal function, and vaccine development, termed immuno-EVs. With seminal studies providing significant progress in the sequential development of engineered EVs as therapeutic anti-tumour platforms, we now require direct assessment to tune and improve the efficacy of resulting immune responses - essential in their translation into the clinic. We believe such a review could strengthen our understanding of the progress in EV immunobiology and facilitate advances in engineering EVs for the development of novel EV-based immunotherapeutics as a platform for cancer treatment.

Keywords:  cancer; extracellular vesicles; immunity; immunoregulation; immunosurveillance; microenvironment; nanovesicles; vaccine

DOI:  https://doi.org/10.1016/j.semcancer.2023.02.002